Toru Sasaki

Budding yeast Dsk2p is a polyubiquitin-binding protein that can interact with the proteasome

Dsk2p from Saccharomyces cerevisiae belongs to the class of proteins that contain a ubiquitin-like (UbL) domain at the N terminus together with a ubiquitin-associated (UBA) domain at the C terminus. We show here that the C-terminal UBA domain of Dsk2p binds to K48-linked polyubiquitin chains, and the N-terminal UbL domain of Dsk2p interacts with the proteasome. Overexpression of Dsk2p caused the accumulation of large amounts of polyubiquitin, and extragenic suppressors of the Dsk2p-mediated lethality proved to be temperature-sensitive mutations in two proteasome subunits, rpn1 and pre2. K48-linked ubiquitin-dependent degradation was impaired by disruption of the DSK2 gene. These results indicate that Dsk2p is K48-linked polyubiquitin-binding protein and also interacts with the proteasome. We discuss a possible role of adaptor function of Dsk2p via its UbL and UBA domains in the ubiquitin-proteasome pathway.

Global stability of models of humoral immunity against multiple viral strains

We analyse, from a mathematical point of view, the global stability of equilibria for models describing the interaction between infectious agents and humoral immunity. We consider the models that contain the variables of pathogens explicitly. The first model considers the situation where only a single strain exists. For the single strain model, the disease steady state is globally asymptotically stable if the basic reproductive ratio is greater than one. The other models consider the situations where multiple strains exist. For the multi-strain models, the disease steady state is globally asymptotically stable. In the model that does not explicitly contain an immune variable, only one strain with the maximum basic reproductive ratio can survive at the steady state. However, in our models explicitly involving the immune system, multiple strains coexist at the steady state.

Global stability of pathogen-immune dynamics with absorption

In this paper, we consider the global stability of the models which incorporate humoural immunity or cell-mediated immunity. We consider the effect of loss of a pathogen, which is called the absorption effect when it infects an uninfected cells. We construct Lyapunov functions for these models under some conditions of parameters, and prove the global stability of the interior equilibria. It is impossible to remove the condition of parameters for the model incorporating humoural immunity.

Massive eosinophilic infiltration in a patient with the nephrotic syndrome and drug-induced interstitial nephritis

The pathologic feature of acute interstitial nephritis is the infiltration of mononuclear cells, predominantly lymphocytes and monocytes, into the interstitium. We present an unusual case of a 49-year-old man with drug-induced acute interstitial nephritis whose renal biopsy specimen showed a massive infiltration of eosinophils into the interstitium and eosinophils infiltrating into the glomerulus through a gap in Bowmans capsule and the juxtaglomerular zone. The patient initially was referred to us with a recurrence of the nephrotic syndrome. Deterioration of renal function and an increase in proteinuria was noted at that time. Triazolam, a sleep inducer, was the suspected cause of the acute interstitial nephritis. Renal biopsy revealed sclerotic glomeruli containing eosinophils among massive infiltrated eosinophils and a loss of endothelial cells and mesangial cells in contrast to a preservation of epithelial cells. Infiltrating eosinophils were directly attached to the glomerular basement membrane, and free granules from the eosinophils were observed in the capillary lumen. In addition to chronic sclerotic change, eosinophils may have further damaged the glomerular capillary wall, leading to an increased severity of proteinuria in this case.

Construction of Lyapunov functions for some models of infectious diseases in vivo: from simple models to complex models.

We present a constructive method for Lyapunov functions for ordinary differential equation models of infectious diseases in vivo. We consider models derived from the Nowak-Bangham models. We construct Lyapunov functions for complex models using those of simpler models. Especially, we construct Lyapunov functions for models with an immune variable from those for models without an immune variable, a Lyapunov functions of a model with absorption effect from that for a model without absorption effect. We make the construction clear for Lyapunov functions proposed previously, and present new results with our method.

Ubiquitin chains in the Dsk2 UBL domain mediate Dsk2 stability and protein degradation in yeast

Ubiquitin-like (UBL)-ubiquitin-associated (UBA) proteins, including Dsk2 and Rad23, act as delivery factors that target polyubiquitinated substrates to the proteasome. We report here that the Dsk2 UBL domain is ubiquitinated in yeast cells and that Dsk2 ubiquitination of the UBL domain is involved in Dsk2 stability, depending on the Dsk2 UBA domain. Also, Dsk2 lacking ubiquitin chains impaired ubiquitin-dependent protein degradation and decreased the interaction of Dsk2 with polyubiquitinated proteins in cells. Moreover, Dsk2 ubiquitination affected ability to restore the temperature-sensitive growth defect of dsk2Δ. These results indicate that ubiquitination in the UBL domain of Dsk2 has in vivo functions in the ubiquitin-proteasome pathway in yeast.

On the optimal duration of memory of losing a conflict – a mathematical model approach

In male broad-horned flour beetles, Gnatocerus cornutus, losers of conflicts avoid fighting at subsequent encounters. The loser effect lasts for 4 days. It is considered that the memory of losing remains for 4 days. The duration of the memory is expected to affect the fitness, and the duration, 4 days, is expected to be optimal. We consider the fitness of a mutant in an homogeneous population to obtain the optimal duration. Here we carry out simulations using an individual-based model. The results suggest that the trade-off of getting mating chances and avoiding damage can cause the optimal duration of the memory, and that the decay in time of the female population is an important factor.

Global dynamics of B cells and anti-idiotipic B cells and its application to autoimmunity

Global behavior of B models is discussed. When the source term for new B cells equals zero, the system has a conservation quantity. It implies the structurally unstability. It suggests that lack of the source of new B cells may unstabilize the immune system. When the B model incorporates autoimmunity, it loses symmetry. The asymmetry suggests the transition from a tolerant state to autoimmune state is more likely than the inverse transition. Effect of dose of antigen is also considered.

Myeloma kidney associated with acute renal failure after pneumonia.

骨髄腫腎に肺炎を契機に発症した急性腎不全の1例を経験し, 治療により血液透析より離脱し得たので報告する.症例は74歳, 男性. 肺炎に続発して無尿となり補液や利尿剤などの投与を受けた. しかし急性腎不全がさらに進行したため血液透析を開始した. 骨髄穿刺, 血清および尿中免疫電気泳動などで多発性骨髄腫と診断した. 腎機能の回復が遅れていたため腎生検を施行し骨髄腫腎と診断した. そこで化学療法 (MP療法) を開始したところ, 腎機能が次第に回復し血液透析より離脱し得た.多発性骨髄腫の急性腎不全合併例には, 脱水, 感染症, その治療に対する抗生剤, 高カルシウム血症, 造影剤などの誘因に対する処置や, 血液透析や血漿交換などの適切な血液浄化法の選択, および多発性骨髄腫に対する化学療法など, 積極的な治療が重要であると考えられた.