Search

Fewer than half of all patients with advanced-stage high-grade serous ovarian cancers (HGSCs) survive more than five years after diagnosis, but those who have an exceptionally long survival could provide insights into tumor biology and therapeutic approaches. We analyzed 60 patients with advanced-stage HGSC who survived more than 10 years after diagnosis using whole-genome sequencing, transcriptome and methylome profiling of their primary tumor samples, comparing this data to 66 short- or moderate-term survivors. Tumors of long-term survivors were more likely to have multiple alterations in genes associated with DNA repair and more frequent somatic variants resulting in an increased predicted neoantigen load. Patients clustered into survival groups based on genomic and immune cell signatures, including three subsets of patients with BRCA1alterations with distinctly different outcomes. Specific combinations of germline and somatic gene alterations, tumor cell phenotypes and differential immune responses appear to contribute to long-term survival in HGSC.

For liquid crystal elastomers (LCEs), crosslinking is a stress reinforcing factor that sufficiently inhibits macroscopic deformation. In this study, coarse-grained molecular simulations were performed to systematically investigate the dependence of the stress–strain curves of LCEs on the crosslink density. For the unidirectionally oriented initial structure of LCEs, uniaxial elongation was performed in perpendicular or parallel directions. The perpendicularly elongated LCEs demonstrated a characteristic plateau region in the stress–strain curve, indicating soft elasticity. This plateau region corresponds to a large change in the orientational order parameter, indicating that the orientation of mesogens is closely related to soft elasticity. The strain region corresponding to the soft elasticity became narrower as the crosslink density increased. The change in the orientation order parameter also became steeper with increasing crosslink density. On the other hand, the stress values in the plateau region increased with increasing crosslink density. These results indicate a systematic trade-off between stress and strain in the soft elasticity of LCEs, which means that it is possible to select the optimal set of values of stress and the strain range through the crosslink density. Furthermore, the presence of optimal solvent and polymer chain densities that can increase the stress while extending the strain range is indicated.

Order parameters make it possible to quantify the degree of structural ordering in a material and thus to apply as the reaction coordinates during the free-energy analysis of phase or structure transitions. Furthermore, order parameters are useful in determining the local structures of molecular groups during transition stages. However, identifying or developing local order parameters (LOPs) that are sensitive for specific materials and phases is a non-trivial task. In this study, the ability of LOPs to classify the solid and liquid structures of water at coexistence or triple points is investigated with the aid of supervised machine learning. The classification accuracy of a total of 179,738,433 combinations of 493 LOPs is automatically and systematically compared for water structures at the ice Ih–Ic–liquid coexistence point and the ice III–V–liquid and ice V–VI–liquid triple points. The optimal sets of two LOPs are found for each point, and sets of three LOPs are suggested for better accuracy.

Clathrate hydrates are crystalline solids with guest molecules in a hydrogen-bonding network of frozen water. Cyclopropane hydrate has a four-phase coexistence point of guest gas, ice, and two hydrates, suggesting ice–hydrate and hydrate–hydrate structural transitions, but little is known about the details. Microscopic approaches such as molecular simulations are expected as a means of elucidation, but these require reaction coordinates that are sensitive to structural changes (e.g., order parameters). Here, 1220 local order parameters (LOPs) and their combinations were used to classify cyclopropane hydrate and ice structures in the vicinity of the four-phase coexistence point. A total of 21 599 490 LOP combinations were automatically and systematically evaluated via supervised machine learning. The optimal (set of) LOP(s) distinguished between structure I and structure II cyclopropane hydrates and ice Ih with high accuracy and robustness.

Isotropic periodic sum (IPS) is a technique that calculates long-range interactions differently than conventional lattice sum methods. The difference between IPS and lattice sum methods lies in the shape and distribution of remote images for long-range interaction calculations. The images used in lattice sum calculations are identical to those generated from periodic boundary conditions and are discretely positioned at lattice points in space. The images for IPS calculations are “imaginary”, which means they do not explicitly exist in a simulation system and are distributed isotropically and periodically around each particle. Two different versions of the original IPS method exist. The IPSn method is applied to calculations for point charges, whereas the IPSp method calculates polar molecules. However, both IPSn and IPSp have their advantages and disadvantages in simulating bulk water or water–vapor interfacial systems. In bulk water systems, the cutoff radius effect of IPSn strongly affects the configuration, whereas IPSp does not provide adequate estimations of water–vapor interfacial systems unless very long cutoff radii are used. To extend the applicability of the IPS technique, an improved IPS method, which has better accuracy in both homogeneous and heterogeneous systems has been developed and named the linear-combination-based isotropic periodic sum (LIPS) method. This improved IPS method uses linear combinations of basis potentials. We performed molecular dynamics (MD) simulations of bulk water and water–vapor interfacial systems to evaluate the accuracy of the LIPS method. For bulk water systems, the LIPS method has better accuracy than IPSn in estimating thermodynamic and configurational properties without the countercharge assumption, which is used for IPSp. For water–vapor interfacial systems, LIPS has better accuracy than IPSp and properly estimates thermodynamic and configurational properties. In conclusion, the LIPS method can successfully estimate homogeneous and heterogeneous systems of polar molecular systems with good accuracy.

AbstractWe evaluated the contribution of seed dispersal by birds to the colonization of fleshy-fruited plants beneath plants that bear fleshy fruits and were used as perches by birds. Specifically, we investigated the composition of seeds and saplings sampled beneath nine fleshy-fruited perch plant species in a Pinus thunbergiistand on a coastal sand dune in central Japan. Both the numbers and the species numbers of bird-dispersed (pulpless) seeds differed significantly among the perch plant species. Nevertheless, the quantitative compositions of bird-dispersed seeds were similar among the perch plant species because of the significant positive interspecific correlations of species rank order in numbers of bird-dispersed seeds per species. Similar relationships were also found for saplings. For each perch plant species, the numbers of fallen conspecific seeds were significantly higher than or not different from those of heterospecific seeds. Furthermore, the numbers of pulpy seeds that fell directly from the perch plant were significantly higher than those of bird-dispersed conspecific seeds for seven of nine perch plant species. However, the densities of conspecific saplings were significantly lower than those of heterospecific saplings. Most pulpy seeds, therefore, probably do not germinate beneath their mother plants, and conspecific seeds probably accumulate in seed banks or are consumed by herbivores.

An experiment was undertaken to determine if dietary conjugated linoleic acid (CLA) influences the early stage of the inflammatory response caused by a single injection of Salmonella enteritidisilipopolysaccharide (LPS) in male broiler chicks. Chicks (7 days old) were fed either 0 or 10 g CLA/kg in their diet for 21 days. At 28 days old, birds were injected intraperitoneally with 1.5 mg LPS/kg body weight after 12 h fasting. Changes in feed intake, rectal temperature and plasma α‐1 acid glycoprotein and ceruloplasmin concentrations were measured during 24 h after LPS injection. Chicks fed the CLA diet were fed more feed for 24 h, had a lower rectal temperature at 9 and 24 h and a lower plasma α‐1 acid glycoprotein concentration at 24 h after LPS injection than chicks fed the basal diet. Plasma ceruloplasmin concentration tended to be lower in chicks fed the CLA diet than in chicks fed the basal diet. The results suggest that dietary CLA alleviate undesirable early inflammatory response due to LPS injection in male broiler chicks.

We and others have previously reported a hepatitis B virus (HBV)-like hepadnavirus strain which seemed to be indigenous to West African chimpanzees (Pan troglodytes verus). After that, we obtained an HBsAg-positive serum sample from a chimpanzee from Central Africa, named Bassi, belonging to another subspecies (P. troglodytes troglodytes). The full-genome nucleotide sequence of the hepadnavirus from Bassi showed a significant difference (9–26%) from those so far reported from primates including humans, chimpanzees and gorillas, suggesting a novel strain. More interestingly, however, the core antigen (HBcAg) deduced from Bassi’s sequence showed only 78–82% similarity to known primate strains at the amino acid level, whereas the other strains shared more than 90% similarity. HBcAg expressed from Bassi HBV failed to react with monoclonal antibodies that were directed at an epitope borne by codons 135–145 of HBcAg of conventional hepadnaviruses. This could explain why Bassi was negative for anti-HBc in a routine test. Here we report the novel HBV strain presumably indigenous to P. troglodytes troglodytesin Central Africa.

We identified hepatitis E virus (HEV) RNA in serum from a Japanese patient with acute hepatitis, who had never been abroad. The full-genome nucleotide sequence of the HEV isolate (JRA1) from this patient was composed of 7227 nucleotides excepting the poly(A) tail and had ORF1 coding for 1703 amino acids (aa), ORF2 coding for 660 aa, and ORF3 coding for 122 aa. This Japanese strain showed approximately 87% nucleotide similarity to human and swine strains reported from the United States, while it had only 73–76% similarity to Asian and Mexican strains. Here we report the characteristics of the HEV-JRA1 isolate, which might be the first example of an indigenous strain(s) of HEV in Japan.

TT virus (TTV) is a common virus and consists of many genotypes and variants. In addition, there exists a virus which both differs greatly from and retains a considerable resemblance to TTV, such as the TTV-like mini virus (TLMV) as we reported previously. Here we report the near full length genomic sequences of 4 isolates of a new variant of TTV (designated YONBAN) along with the full length sequences of 2 isolates of the TTV-SANBAN lineage and 7 isolates of the TLMV species derived from human sera. The TTV-YONBAN sequences showed only about 50% identity at the nucleotide level to those of the prototype TTV (TA278) and to SANBAN, and even less to TLMV. Moreover, the ORF1 of YONBAN lacked the ATG initiation codon which is shared by all the TTV and TLMV isolates so far identified in humans; instead, YONBAN had a Kozak’s rule-compatible ACG codon as the candidate initiation site for the ORF1 translation. Nevertheless, the overall genetic structure and the conserved amino acid motifs within the ORF1 and the ORF2 were well shared among the prototype TTV strains, the SANBAN and YONBAN variants, and TLMV. The most conserved nucleotide sequence was found in the noncoding region just upstream from the ORF2, allowing construction of a phylogenetic tree which implied that the TTV genotypes and variants, the TLMV, and chicken anemia virus could be coclassified under a superfamily for which we proposed the name of ‘Paracircoviridae’ in our previous report.

Among the many mutations found in the hepatitis B virus (HBV) genome, some have been associated with fulminant hepatitis, as exemplified by precore‐defective mutations. The aim of this study was to determine whether such mutations also are found in Vietnamese cases of fulminant hepatitis B. The full‐genome nucleotide sequence of HBV in three patients with fulminant hepatitis (F‐2, F‐3, and F‐6) and one with acute hepatitis (A‐3), who were admitted to Cho Ray Hospital, Ho Chi Minh City, Vietnam was ascertained. Additionally, two patients with fulminant hepatitis (F‐1 and F‐7) and three with acute hepatitis (A‐1, A‐2, and A‐5) were examined only for the precore/core region of HBV. Remarkably, the nonsense mutation at precore codon 28 (Trp82Stop) was found in four of the five patients with fulminant hepatitis, while all the acute hepatitis patients harbored wild type (one had a mixture of wild and mutant types). The missense mutations within the core region, Ile97Leu and Pro130Ile/Thr/Ser, were also remarkable in fulminant hepatitis. Only F‐2 was free from these precore/core mutations, but F‐2 was unique in that it possessed a chimeric genotype: it could be classified into genotype C as a whole, but its X region was of genotype B, like the other four fulminant hepatitis isolates (F‐1, F‐3, F‐6, and F‐7). The codon 41 of the X protein was Pro in all three fulminant hepatitis cases examined for this region, while it was Ser in the wild‐type isolates of genotype B. Of note as negative data, the mutations C1653T and T1753M of the enhancer II (Enh II) and A1762T and G1764A of the precore/core promoter regions, once reported to be relevant to severe or fulminant hepatitis, were not found in the present cases. The results with the Vietnamese cases of fulminant hepatitis corroborated results of previous studies with respect to the mutations Trp28Stop of precore and Ile97Leu and Pro130Ile/Thr/Ser of core, but not for the mutations within Enh II and precore/core promoter region. Whether the Ser41Pro mutation in the X region of genotype B HBV is Vietnam‐specific or disease‐specific deserves further investigation. J. Med. Virol. 61:23–28, 2000. © 2000 Wiley‐Liss, Inc.

Hepatitis B virus (HBV) belongs to the genus Orthohepadnavirusof the family Hepadnaviridae. Having been found in various animals (duck, heron, woodchuck, ground squirrel, and primates), hepadnaviruses must have undergone a long history of evolution and may comprise more members than currently recognized. Chimpanzees may also have their own hepadnavirus, even if it might be very close to HBV. We analyzed HBV-like sequences from three chimpanzees (Pan troglodytes) that were most likely infected during their life in Africa in the wild. Two chimpanzees (Ch256 and Ch258) possessed a viral genome of 3182 nt in length with a 33-nt deletion in the preS1 region, which could not be classified into any of the six genotypes (A–F) of human HBV but was very homologous to a previously reported isolate from a London Zoo chimpanzee. Phylogenetically distinct from the HBV-like sequences from gibbons, orangutans, and a gorilla so far reported, the Ch256 and Ch258 isolates would represent an indigenous chimpanzee HBV (tentatively ChHBV). A third chimpanzee (Ch195) had a 3212-nt genome, classifiable into the genotype E of HBV. Because HBV-E has been found mostly in Africans, Ch195 may have been infected from a human source in Africa. However, an inverse scenario is also possible: a spread of HBV-E might have occurred from chimpanzees to humans a long time ago in Africa. Analysis of the arginine-rich C-terminal region of the core protein, which is well conserved among mammalian hepadnaviruses, indicated that HBV-E/F and nonhuman primate hepadnaviruses are much closer than HBV-A/B/C/D to the hepadnaviruses of woodchuck and ground squirrel. Our results support an “ex-nonhuman primate” hypothesis for the origin of HBV.

Information on the entire genome of TT virus (TTV) has been scarce. The circular ssDNA genome of a variant (isolate name SANBAN) that we sequenced was only 56.7% homologous to the prototype isolate (TA278), with even lower homology at the amino acid level: 34.2% for ORF1 and 39.7% for ORF2. Regarding the ORF1, SANBAN was only very distantly related to the six major TTV genotypes reported to date. In partial ORF2 sequences determined on 44 isolates taken together, TTV has a broad range of genetic diversity and the SANBAN isolate may represent a new TTV-like viral species or genus and not merely a genotype of TTV.

The present study was undertaken to determine sperm motility and counts in semen yielded by para-chloroamphetamine (PCA)-induced ejaculation of aged rats which had lost their reproductive ability, and to attempt artificial insemination with suspensions of spermatozoa obtained in this way. The semen yielded by PCA-induced ejaculation from aged (75-week-old) rats had average sperm counts of 0.82±0.69 × 107, which were much lower than the average counts (9.42±1.65 × 107) for semen spontaneously ejaculated by young adult rats (14 weeks old). However, 77.5% of the spermatozoa contained in the PCA-induced semen were rated as showing the most active movement. Spermatozoa collected in this way were injected into the upper parts of both uterine horns or into both ovarian bursae. Both methods made the females pregnant, but the results were better after injection into the ovarian bursae. The offspring born to these females showed no abnormalities.

There is no report on the fine structure of three types of olfactory organs in Xenopus laevis. Their functional assignments in olfaction are not yet established. The fine structure of three types of olfactory organs, olfactory epithelium (OE), vomeronasal organ (VNO), and middle chamber epithelium (MCE), was examined in Xenopus laevis by light and electron microscopy. The olfactory cells of the OE and the sensory cells of the VNO were equipped with cilia and microvilli, respectively, similar to terrestrial animals that possess both the OE and the VNO. On the other hand, the sensory cells of the MCE were classified into two types, the sensory cells with cilia and the sensory cells with microvilli, like those of the OE in fish. These findings suggest that the OE and the VNO in Xenopus laevis detect different kinds of odoriferous molecules in air, whereas the MCE is involved in the perception of odorants in water. Anat. Rec. 252:301–310, 1998. © 1998 Wiley-Liss, Inc.

Summary: Utilizing a highly sensitive radioimmunoassay, hepatitis Be antigen (HBeAg) was detected in the cord serum of eight out of nine babies born to mothers who carried hepatitis B surface antigen together with HBeAg. The titer of HBeAg in the cord serum was much lower than that in the corresponding maternal serum, and escaped the detection by the conventional micro-Ouchterlony immunodiffusion. HBeAg in maternal and cord sera was fractionated into free and IgG-bound moieties by salt precipitation, and their proportion was compared in four pairs. In every pair tested, both free and IgG-bound HBeAg were found in the maternal serum, but only IgG-bound HBeAg was detected in the corresponding cord serum. Based on these results, IgG-bound HBeAg can be transmitted through the placenta, but free HBeAg may barely pass the placenta despite its much smaller size.Speculation: Among macromolecules present in the maternal circulation, only IgG is known to be transmitted into fetal circulation. The presence of IgG-bound HBeAg, but not of free HBeAg, in the cord serum of babies born to HBeAg-positive mothers suggests that IgG would be responsible for the materofetal transmission of HBeAg.

There is no report on the fine structure of three types of olfactory organs in Xenopus laevis. Their functional assignments in olfaction are not yet established. The fine structure of three types of olfactory organs, olfactory epithelium (OE), vomeronasal organ (VNO), and middle chamber epithelium (MCE), was examined in Xenopus laevisby light and electron microscopy. The olfactory cells of the OE and the sensory cells of the VNO were equipped with cilia and microvilli, respectively, similar to terrestrial animals that possess both the OE and the VNO. On the other hand, the sensory cells of the MCE were classified into two types, the sensory cells with cilia and the sensory cells with microvilli, like those of the OE in fish. These findings suggest that the OE and the VNO in Xenopus laevisdetect different kinds of odoriferous molecules in air, whereas the MCE is involved in the perception of odorants in water. Anat. Rec. 252:301–310, 1998. © 1998 Wiley‐Liss, Inc.

The purpose of this study was to determine whether diet composition would influence calcium and phosphorus metabolism in chicks administered estrogen. At 1 day of age, broiler chicks were fed either a corn-soybean meal diet (CS), or an isoenergetic and isonitrogenous diet containing 5% fish meal, 5% alfalfa meal and 10% torula yeast (FAY). At 21 days equivalent numbers were implanted with one of two lengths of Silastic tubing containing estradiol dipropionate, while the remaining birds served as nonimplanted controls. Significant increases were observed in liver weight, liver lipid, plasma total calcium and inorganic phosphate in chicks that were implanted, while concomitant declines were seen in body weight. Implanted chicks fed the CS diet had significantly higher liver weight, liver lipid, plasma phosphorus and plasma calcium and lower tibial bone ash than those fed the FAY diet. Furthermore, liver lipid values were very highly correlated with plasma phosphorus and calcium. In an identical study with slower growing White Leghorn chicks, the same trends were observed but were less well defined. These data show that the inclusion of certain ingredients into corn-soybean diets balanced for the major nutrients affects the response of chicks to estrogenization. Liver lipid deposition, calcium and phosphorus metabolism are all subject to diet and estrogen interactions.

Injecting White Leghorn chicks every other day with 20 mg ascorbic acid significantly reduced the increase in liver weight and lipids caused by feeding a diet with 0.1% dienestrol diacetate. In chicks fed two different basal diets containing 0.1% dienestrol diacetate, injecting chicks every other day with 20 mg α-tocopherol did not significantly reduce liver weight or lipids while the ascorbic acid injections did. Injecting meat-type chicks implanted with estradiol with 10 mg ascorbic acid daily significantly reduced liver weight, liver lipids, and plasma estradiol, but injecting with 8 mg α-tocopherol daily had no significant effect.

The efficacy of hepatitis B immune globulin (HBIG) with two hepatitis B virus (HBV) vaccines was investigated for prevention of vertical transmission of HBV to infants born to e antigen-positive HBV carrier mothers. Infants received 150 mg of the F(ab′)2, fraction of HBIG intravenously within 2 hr of delivery, and serum titers of antibody to hepatitis B surface antigen (anti-HBs) were kept >1:4 (passive hemagglutination) by subcutaneous injection of HBIG thereafter. HBV vaccine was started three or six months after delivery. Of 50 infants older than nine months, 49 were actively immunized against hepatitis B surface antigen. Vaccine containing alum adjuvant immunized the infants in a shorter period than did vaccine without adjuvant. Serum titers of anti-HBs of actively immunized infants were well maintained afterward. None of the infants treated with HBIG and HBV vaccine was positive for serum antibody to hepatitis B core antigen at 12 months of age. No side effects were observed.