STUDIES ON TOXOPLASMOSIS II. : SOME OBSERVATIONS ON STRAIN "HT" WHICH WAS ISOLATED FROM A HARE (LEPUS TIMIDUS AINU) IN SAPPORO

The hare strain HT of Toxoplasma gondii which was reported in the previous paper was tested immunologically and also pathogenicity for the laboratory animals and was examined in comparison with known toxoplasma strain RH. The data obtained are summarized as follows. 1. The strain HT indicated high virulence for mice and death occurred generally in 5∿6 days after intraperitoneal inoculation, almost the same as the RH; however the number of parasites in mouse peritoneal fluid was very small in comparison with the strain RH. 2. For rabbit and guinea pig, the strain showed very low virulence. In rabbit, even resulting from intracerebral inoculation, only fever reaction occurred and the general conditions ran always normal afterward. 3. Immunologically, by the use of cross complement-fixation test, this strain was identified as Toxoplasma gondii. 4. At first, the isolated strain HT had revealed no reactivity in vitro in case of dye test with the rabbit sera infected with the strains HT and RH, however the isolated strain had showed the ability to produce cytoplasm-modifying antibody reacting with the antigen RH. After about more than 50 mouse passages, the strain revealed reactivity in vitro the same as the strain RH. The above facts must be remembered for serological identification of the newly isolated strains by the dye test

The upstream sequence element of the C2 complement poly(A) signal activates mRNA 3′ end formation by two distinct mechanisms

The poly(A) signal of the C2 complement gene is unusual in that it possesses an upstream sequence element (USE) required for full activity in vivo. We describe here in vitro experiments demonstrating that this USE enhances both the cleavage and poly(A) addition reactions. We also show that the C2 USE can be cross-linked efficiently to a 55-kD protein that we identify as the polypyrimidine tract-binding protein (PTB), implicated previously in modulation of pre-mRNA splicing. Mutation of the PTB-binding site significantly reduces the efficiency of the C2 poly(A) site both in vivo and in vitro. Furthermore, addition of PTB to reconstituted processing reactions enhances cleavage at the C2 poly(A) site, indicating that PTB has a direct role in recognition of this signal. The C2 USE, however, also increases the affinity of general polyadenylation factors independently for the C2 poly(A) signal as detected by enhanced binding of cleavage-stimulaton factor (CstF). Strikingly, this leads to a novel CstF-dependant enhancement of the poly(A) synthesis phase of the reaction. These studies both emphasize the interconnection between splicing and polyadenylation and indicate an unexpected flexibility in the organization of mammalian poly(A) sites

Clinical Characteristics and Diagnostic Prediction of Severe Fever with Thrombocytopenia Syndrome and Rickettsiosis in the Co-Endemic Wakayama Prefecture, Japan

Background and Objectives: The Wakayama prefecture is endemic for two types of tick-borne rickettsioses: Japanese spotted fever (JFS) and scrub typhus (ST). Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne hemorrhagic viral disease with a high mortality rate and is often difficult to differentiate from such rickettsioses. SFTS cases have recently increased in Wakayama prefecture. For early diagnosis, this study aimed to evaluate the clinical characterization of such tick-borne infections in the co-endemic area. Materials and Methods: The study included 64 febrile patients diagnosed with tick-borne infection in Wakayama prefecture between January 2013 and May 2022. Medical records of 19 patients with SFTS and 45 with rickettsiosis (JSF, n = 26; ST, n = 19) were retrospectively examined. The receiver operating curve (ROC) and area under the curve (AUC) were calculated to evaluate potential factors for differentiating SFTS from rickettsiosis. Results: Adults aged ≥70 years were most vulnerable to tick-borne infections (median, 75.5 years; interquartile range, 68.5–84 years). SFTS and rickettsiosis occurred mostly between summer and autumn. However, no significant between-group differences were found in age, sex, and comorbidities; 17 (89%) patients with SFTS, but none of those with rickettsiosis, experienced gastrointestinal symptoms such as vomiting, abdominal pain, and diarrhea. Meanwhile, 43 (96%) patients with rickettsiosis, but none of those with SFTS, developed a skin rash. The AUCs of white blood cells (0.97) and C-reactive protein (CRP) levels (0.98) were very high. Furthermore, the differential diagnosis of SFTS was significantly associated with the presence of gastrointestinal symptoms (AUC 0.95), the absence of a skin rash (AUC 0.98), leukopenia 9/L (AUC 0.95), and low CRP levels p Conclusions: Clinical characteristics and standard laboratory parameters can verify the early diagnosis of SFTS in areas where tick-borne infections are endemic

A Core Complex of CPSF73, CPSF100, and Symplekin May Form Two Different Cleavage Factors for Processing of Poly(A) and Histone mRNAs

Metazoan histone mRNAs are unique: their pre-mRNAs contain no introns and the mRNAs are not polyadenylated ending instead in a conserved stem-loop structure. In Drosophila, canonical poly(A) signals are located downstream of the normal cleavage site of each histone gene, and are utilized when histone 3’end formation is inhibited. Here we define a sub-complex of poly(A) factors required for histone pre-mRNA processing. We demonstrate that Symplekin, CPSF73 and CPSF100 are present in a stable complex and interact with histone specific processing factors. We use chromatin immunoprecipitation to show that Symplekin and CPSF73, but not CstF50, cotranscriptionally associate with histone genes. Depletion of SLBP recruits CstF50 to histone genes. Knockdown of CPSF160 or CstF64 downregulates Symplekin but does not affect histone pre-mRNA processing or association of Symplekin with the histone locus. These results suggest that a common core cleavage factor is required for processing of histone and polyadenylated pre-mRNAs