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Climate change is predicted to increase atmospheric vapor pressure deficit, exacerbating soil drought, and thus enhancing tree evaporative demand and mortality. Yet, few studies have addressed the longer-term drought acclimation strategy of trees, particularly the importance of morphological versus hydraulic plasticity. Using a long-term (20 years) irrigation experiment in a natural forest, we investigated the acclimation of Scots pine (Pinus sylvestris) morpho-anatomical traits (stomatal anatomy and crown density) and hydraulic traits (leaf water potential, vulnerability to cavitation (Ψ50), specific hydraulic conductivity (Ks), and tree water deficit) to prolonged changes in soil moisture. We found that low water availability reduced twig water potential and increased tree water deficit during the growing season. Still, the trees showed limited adjustments in most branch-level hydraulic traits (Ψ50 and Ks) and needle anatomy. In contrast, trees acclimated to prolonged irrigation by increasing their crown density and hence the canopy water demand. This study demonstrates that despite substantial canopy adjustments, P. sylvestris may be vulnerable to extreme droughts because of limited adjustment potential in its hydraulic system. While sparser canopies reduce water demand, such shifts take decades to occur under chronic water deficits and might not mitigate short-term extreme drought events., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Recent experiments have underlined the potential of δ2H in tree-ring cellulose as a physiological indicator of shifts in autotrophic versus heterotrophic processes (i.e., the use of fresh versus stored non-structural carbohydrates). However, the impact of these processes has not yet been quantified under natural conditions. Defoliator outbreaks disrupt tree functioning and carbon assimilation, stimulating remobilization, therefore providing a unique opportunity to improve our understanding of changes in δ2H. By exploring a 700-year tree-ring isotope chronology from Switzerland, we assessed the impact of 79 larch budmoth (LBM, Zeiraphera griseana [Hübner]) outbreaks on the growth of its host tree species, Larix decidua [Mill]. The LBM outbreaks significantly altered the tree-ring isotopic signature, creating a 2H-enrichment and an 18O- and 13C-depletion. Changes in tree physiological functioning in outbreak years are shown by the decoupling of δ2H and δ18O (O-H relationship), in contrast to the positive correlation in non-outbreak years. Across the centuries, the O-H relationship in outbreak years was not significantly affected by temperature, indicating that non-climatic physiological processes dominate over climate in determining δ2H. We conclude that the combination of these isotopic parameters can serve as a metric for assessing changes in physiological mechanisms over time., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Insect defoliation impacts forest productivity worldwide, highlighting the relevance of plant-insect interactions. The larch budmoth (Zeiraphera griseana Hübner) is one of the most extensively studied defoliators, where numerous tree ring-based analyses on its host (Larix decidua Mill.) have aided in identifying outbreak dynamics over the past millennia. Yet, outbreaks have been widely absent after the early 1980s, and little is known about the in situ tree physiological responses and the allocation of carbon resources during and after defoliation. In summer 2018, we tracked an ongoing larch budmoth outbreak in a well-studied larch forest in the Swiss Alps. We performed biweekly monitoring on an affected and unaffected site using a unique combination of xylogenesis observations, measurements of non-structural carbohydrates, isotopic analysis of needle assimilates and ground-based and remote-sensed leaf trait observations. The budmoth induced a defoliation that lasted 40 days and could be detected by satellite observations. Soluble sugars significantly decreased in needles and stem phloem of the defoliated trees, while starch levels remained stable in the stem and root xylem compared to the control. Carbon and oxygen isotope ratios in needle assimilates indicated that neither photosynthetic assimilation rates nor stomatal conductance was different between sites before, during and after the outbreak. Defoliated trees ceased cell wall thickening 17 days earlier than unaffected trees, showing the earliest halt of ring formation recorded from 2007 untill 2013 and causing significant thinner cell walls, particularly in the latewood. No significant differences were found for cell enlargement rates and ring width. Our study revealed that an outbreak causes a downregulation of cell wall thickening first, while no starch is mobilized or leaf physiology is adjusted to compensate for the reduced carbon source due to defoliation. Our observations suggest that affected larch trees prioritize leaf recovery and carbon storage over wood biomass development., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

During the growing season, trees allocate photoassimilates to increase their aboveground woody biomass in the stem (ABIstem). This 'carbon allocation' to structural growth is a dynamic process influenced by internal and external (e.g., climatic) drivers. While radial variability in wood formation and its resulting structure have been intensively studied, their variability along tree stems and subsequent impacts on ABIstem remain poorly understood. We collected wood cores from mature trees within a fixed plot in a well-studied temperate Fagus sylvatica L. forest. For a subset of trees, we performed regular interval sampling along the stem to elucidate axial variability in ring width (RW) and wood density (ρ), and the resulting effects on tree- and plot-level ABIstem. Moreover, we measured wood anatomical traits to understand the anatomical basis of ρ and the coupling between changes in RW and ρ during drought. We found no significant axial variability in ρ because an increase in the vessel-to-fiber ratio with smaller RW compensated for vessel tapering towards the apex. By contrast, temporal variability in RW varied significantly along the stem axis, depending on the growing conditions. Drought caused a more severe growth decrease, and wetter summers caused a disproportionate growth increase at the stem base compared with the top. Discarding this axial variability resulted in a significant overestimation of tree-level ABIstem in wetter and cooler summers, but this bias was reduced to ~2% when scaling ABIstem to the plot level. These results suggest that F. sylvatica prioritizes structural carbon sinks close to the canopy when conditions are unfavorable. The different axial variability in RW and ρ thereby indicates some independence of the processes that drive volume growth and wood structure along the stem. This refines our knowledge of carbon allocation dynamics in temperate diffuse-porous species and contributes to reducing uncertainties in determining forest carbon fixation., (© The Author(s) 2020. Published by Oxford University Press.)

HealthNuts is a single-centre, multi-wave, population-based longitudinal study designed to assess prevalence, determinants, natural history and burden of allergy (particularly food allergy) in the early years of life. It is novel in the use of serial food challenge measures within its population frame to confirm food allergy. The cohort comprises 5276 children initially recruited at age 12 months from council-run immunization sessions across Melbourne, Australia. As well as parent-completed questionnaires and researcher-observed eczema status, all infants underwent skin-prick testing to egg, peanut, sesame and either cow's milk or shellfish, and those with detectable wheals underwent food challenges to determine clinical allergy. In wave 2, conducted at age 4 years, validated questionnaires collected data on asthma, allergic rhinitis (hay fever), eczema and food allergies. Food challenges were repeated in children previously identified as food allergic to determine resolution. In wave 3, all children (irrespective of food allergy status) were invited for clinical assessment at age 6 years, including lung function, physical measurements, skin-prick testing to foods and aeroallergens and food challenges if food sensitized. Biological specimens (blood, cheek swabs) were collected at each wave for ancillary immunological, genetic and epigenetic studies. Applications to access data and/or samples can be submitted to [katrina.allen@mcri.edu.au]., (© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

In April 1996, laboratory testing of imported nonhuman primates (as mandated by quarantine regulations) identified 2 cynomolgus macaques (Macaca fascicularis) infected with Ebola (subtype Reston) virus in a US-registered quarantine facility. The animals were part of a shipment of 100 nonhuman primates recently imported from the Philippines. Two additional infected animals, who were thought to be in the incubation phase, were identified among the remaining 48 animals in the affected quarantine room. The other 50 macaques, who had been held in a separate isolation room, remained asymptomatic, and none of these animals seroconverted during an extended quarantine period. Due to the rigorous routine safety precautions, the facility personnel had no unprotected exposures and remained asymptomatic, and no one seroconverted. The mandatory quarantine and laboratory testing requirements, put in place after the original Reston outbreak in 1989-1990, were effective for detecting and containing Ebola virus infection in newly imported nonhuman primates and minimizing potential human transmission.

The authors studied serial hepatic biopsies of five patients who developed hepatic failure following jejunoileal bypass for extreme obesity, with autopsies of two. The hepatic histologic changes included centrilobular or focal alcoholic hyalin, intrasinusoidal collagenosis, fatty hydropic degeneration, and neutrophilic infiltrate. At least two of the patients were abstinent from alcohol, both prior to and after the surgical procedures. The others, after the bypass procedures, had reduced alcohol consumption from previous levels. All patients developed hepatic failure and histologically progressive hepatic disease with alcoholic hyalin and other changes indistinguishable from alcoholic hepatic disease in 21/2 to 5 months, in spite of hyperalimentation and re-establishment of intestinal continuity in four. Nausea, vomiting, abdominal pain and ascites were prominent complaints. Four of the five patients died in hepatic failure. The authors conclude that these cases of progressive hepatic disease with histologic changes simulating those found in livers of alcoholic patients offer evidence that heavy alcohol consumption may affect the liver in an indirect fashion.

Delayed-type hypersensitivity (DTH), assayed by footpad swelling, was induced in 6- to 8-week-old BALB/cCr mice immunized with formalin-inactivated, sucrose-banded murine type-C viruses. The DTH response was inducible with as little as 11.25 mug sensitizing antigen, was greatest after sc sensitization as compared to im and ip sensitization, and was optimally elicited with a 7-day challenge. A statistical evaluation of the DTH assay revealed that the test was consistently reproducible and limited only by biologic variability of the mouse and the standardization of the antigen preparation. The DTH response was specific for type-C virus subtypes because it could distinguish the Rauscher strain of murine leukemia virus from AKR leukemia virus when the challenge antigen was extracted with Tween 80-ether. Immunized mice that gave DTH responses were resistant to challenge with exogenous, live murine leukemia viruses.

Proliferation of bile ductules is commonly seen in expanded portal tracts and periportal areas in many conditions, including advanced alcoholic liver disease. Such ductules are usually tortuous and irregular and composed of cuboidal cells. They frequently have poorly defined lumens. The epithelial cells are similar to those of normal bile ductules and small bile ducts; however, cells that appear intermediate between duct epithelial cells and hepatocytes are frequently identified by light and electron microscopy. The origin of the ductular cells from hepatocytes may be confirmed by the demonstration of the markers of hepatocytes, such as glycogen and glucose-6-phosphatase activity in some proliferated bile ductules. In addition, alcoholic hyalin is occasionally recognizable in the epithelial cells of bile ductules. The majority of periportal bile ductules appears to have been derived from transformation of hepatic cords rather than multiplication of preexisting bile ducts. The proliferated bile ductules seem to communicate between the bile canaliculi and the interlobular bile ducts.

A sensitive method for demonstrating the site of hepatitis B surface antigen (HBsAg) in fixed tissues embedded in either paraffin or araldite is described. The method employs the peroxidase-rabbit antiperoxidase linkage through goat antirabbit to rabbit anti-HBsAg. In staining hepatitis antigen in agar, comparison of fixation (using three common fixatives) with unfixed precipitation arcs revealed no recognizable differences in antigenicity induced by fixation. The method allows confirmation of positive reaction by appropriate blocking controls. The technic is compared with the orcein stain of Shikata and found to be somewhat more sensitive but slightly more time-consuming.

Studies of tumor incidence and assorted lesions found in 187 C3H-Avy mice throughout their natural life-spans revealed the following: Hepatocellular carcinomas occurred in 54.3% of males, mammary carcinomas in 95% of females, pancreatic islet cell adenomas in 9.4% of males and in no females, and pancreatic islet cell hyperplasia in 41% of males and 23% of fefemales. Islet cell hyperplasia and adenomas appeared to consist predominantly of alpha and delta cells. Multiple tumors, or hyperplasia, or both, of a single site or of multiple sites occurred as frequently in males as they did in females--49.6% and 51.7% respectively. The most frequent neoplasms were hepatocellular carcinomas and islet cell tumors or hyperplasia in males (45.7%) and multiple mammary tumors in females (30%). Heretofore unreported tumors found in this strain of mouse were 12 islet cell adenomas, 2 spindle cell tumors of the meninges and olfactory lobes, a squamous cell carcinoma of the nasal turbinates, and a schwannoma of the spermatic cord.

Plasma, serum, and a concentrate of factor VIII, implicated in human cases of non-A, non-B (NANB) hepatitis, were inoculated into four chimpanzees. All four animals demonstrated significant elevations of alanine aminotransferase levels within five weeks. After recovery from these NANB hepatitis episodes, the chimpanzees were cross-challenged with different inocula. A second episode of NANB hepatitis occurred after challenge in three animals. Reproducibility of the results was established by reversing the sequence of inoculation in two of the animals. A known infectious concentrate of factor VIII failed to induce hepatitis in a previously infected chimpanzee although the animal remained susceptible to a third inoculum, an event suggesting that the first inoculum might contain the same NANB hepatitis agent as the concentrate of factor VIII, which was supported by results of a subsequent cross-challenge experiment. Reinfection did not occur in two chimpanzees injected with their initial challenge strain of NANB hepatitis virus, providing evidence that strain-specific immunity had been established. Thus, experimental evidence is provided for the presence of two NANB hepatitis agents, supporting clinical and epidemiologic studies that favor the existence of more than one etiologic agent.

In the process of establishing the specificity of direct immunoperoxidase staining of liver tissue for hepatitis B surface antigen (HBsAg), an affinity of free horseradish peroxidase (HRP) for HBsAg in hepatocytes (ground-glass cells) was found. Of 95 patients, the horseradish peroxidase reaction was only positive in the livers of the 35 who were chronically HBsAg seropositive and not in the livers from 60 control patients with alcoholic cirrhosis who were HBsAg seronegative. Comparison studies using the orcein technic and immunoperoxidase methods confirmed the observation that both free horseradish peroxidase (not conjugated to an antibody) and HRP conjugated to an antibody unrelated to HBsAg had an affinity to the cytoplasm of hepatocytes containing HBsAg. The precise nature of this affinity is not known, but it is probably due to a reaction between an activated carbohydrate moiety of horseradish peroxidase and the free amino group of HBsAG.

Corzyme-MTM (Abbott Laboratories, North Chicago, IL), a newly introduced kit for the measurement of serum IgM antihepatitis B core antigen by enzyme immunoassay, was evaluated for the diagnosis of acute B-viral hepatitis (AVH-B). The study included 175 acute viral hepatitis patients with transient hepatitis B surface antigen (HBsAg). Sera from 160 were tested on multiple occasions until their HBsAg cleared. IgM anti-HBc was found in 171 of 175 patients (98.4%) during the acute phase. The serum samples from 42 patients with liver biopsy-proven chronic active hepatitis, type B (CAH-B), and 18 patients with persistent hepatitis, type B (PH-B), were analyzed for the presence of IgM anti-HBc, using the same technic. None of the sera from 42 patients with CAH-B and only 2 of the 18 patients with PHB had IgM anti-HBc. Thus, the measuring IgM anti-HBc using Corzyme-M kit is helpful in the diagnosis of AVH-B and in the discrimination of acute from chronic HBV infections.

Natural tumor incidence and type C virus expression in HIH Swiss and BALB/c mice were investigated. The BALB/c mice showed a moderate incidence of lymphoreticular tumors containing infectious ecotropic virus. A second class of lymphoreticular tumors occurred with approximately the same incidence in both strains; though infectious virus could not be isolated from it, it contained the antigens of a common xenotropic virus. These xenotropic viral antigens were found in all NIH Swiss and BALB/c tumors examined and in normal hematopoietic tissues as well. The relationship between different classes of endogenous viruses and tumor development was discussed.

Two hundred seventy-nine patients who died of hepatocellular carcinoma were autopsied at Los Angeles County--USC Medical Center and the John Wesley--USC Liver Unit from 1949 through 1974, and tissues from 168 of these cases were available for staining for hepatitis B surface antigen (HBSAg). Twenty-one per cent of the livers had stainable HBSAg. There were prominent increases both in total numbers of hepatic cancers and in the percentages that were HBSAg-positive beginning about 1970, but the numbers of hepatocellular carcinomas arising in noncirrhotic livers also increased. From 1969 to 1974, 73% of those who had hepatocellular carcinomas arising to nonalcoholic but cirrhotic livers were HBSAg-positive. Racial differences in the incidences of cirrhosis, the incidences of hepatocellular carcinomas associated with HBSAg were found. The incidences of cirrhosis were: Caucasian 11%; Mexican 12.2%; Negro 5.7:; Oriental 10%. Hepatocellular carcinomas arose in 3.2% of Caucasians who had cirrhosis; 3.6% of Mexicans; 8.3% of Negroes; 47% or Orientals. Ten per cent of Caucasians who had hepatocellular carcinomas in cirrhotic livers were HBSAg-positive; 25% of Negroes; 12% of Mexicans; 47% of Orientals.

A lymphocyte transformation microassay (LTA) was developed from spleen harvests of 6- to 8-week-old BABL/cCr mice. The optimal culture conditions for the microassay were established by measurement of lymphoblastogenesis in response to phytohemagglutin (PHA) and pokeweek mitogen. Immunization, as measured by the LTA, of adult BALB/cCr mice with formalin-inactivated, sucrose-banded, murine type-C viruses was achieved with a three-dose regimen of 200, 100, and 100 mug during 3 successive weeks (Freund's complete adjuvant was used with the first dose). The ip route of immunization induced the best responses in lymphocytes harvested 18 days after the last immunogen was given. The LTA was consistently reproducible, limited only by biological variability of the mouse and the standardization of the antigen preparation. In mice immunized with Rauscher murine leukemia virus (R-MuLV) or AKR MuLV vaccine, the LTA was specific for the C-type virus and could be used to distinguish viral subtypes, because R-MuLV elicited responses significantly different from a B-tropic BALB/c leukemia virus. This specificity was evident when the stimulating antigen was presented as UV-inactivated, sucrose-banded virus or as freeze-thaw extracts of cell infected with MuLV.

The age-related incidence of spontaneously occurring neoplasms and degenerative diseases in the F344 inbred rat strain was established from the histologic examination of tissues from 160 male and 192 female rats kept throughout their natural life-span. The most common neoplasms were leukemias (25%), mammary tumors (females, 40.6%; males, 23.1%), pituitary adenomas (females, 35.9%; males, 23.8%), and testicular interstitial cell tumors (males, 85%). Various less common neoplasms were observed: thyroid interstitial cell tumors, adrenocortical adenomas, carcinomas of the genitourinary tract, representative central nervous system tumors, pheochromocytomas, and tumors of mesodermal origin including mesotheliomas, myoblastomas, fibromas, and fibrosarcomas. Multiple tumor types were found in 176 of the rats; metastatic tumors were uncommon. Degenerative diseases including myocardial degeneration and nephrosis were often observed. The incidence rate of these neoplasms and degenerative diseases generally increased with advancing age of the animals.