STUDIES ON THE BACTERIOPHAGE OF D'HERELLE : XI. AN INQUIRY INTO THE MODE OF ACTION OF ANTIBACTERIOPHAGE SERUM

1. Each bacteriophage is a specific antigen. 2. The antibodies against the bacteriophage are independent of those against the bacterial substrate used in preparing the phage. 3. The reaction of neutralization is closely analogous to that of the neutralization of toxin by antitoxin. 4. The serum of mice experimentally infected with mouse typhoid (M.T.) did not become capable of neutralizing phages acting on the infecting organism. 5. The use of the reaction of neutralization of bacteriophage in the diagnosis of disease as proposed by Sonnenschein seems impractical.     

FURTHER STUDIES ON THE ETIOLOGICAL R?LE OF VIBRIO FETUS

The data bearing on these three cases are quite sufficient to rule out Bacillus abortus as the agent. Not only the cultures and guinea pig tests of fetal tissues and contents of the digestive tract, but also the agglutination and guinea pig tests of the milk, were negative. The same is true of the agglutination tests of the blood serum. Only in one case was the placenta obtained in part. The stained films and the sections from various regions showed no abortion bacilli. Guinea pig tests of placental tissue were negative for Bacillus abortus. On the other hand) minute organisms resembling vibrios were detected in the cytoplasm of endothelial cells within capillaries in the edematous subchorionic tissue. Subsequently the agglutination titer of the blood serum of one of these cases rose to a level indicating infection with Bacillus abortus during the second pregnancy. The peculiar distribution of abortions due to Vibrio fetus among older cows and heifers in this herd, resulting at first in cases among older cows and latterly passing to young stock, may be explained by certain occurrences in the herd itself. It may be assumed that the infection was originally brought in by purchased cows. The young stock is kept segregated from these in a special barn, and when 6 months old it is pastured on outlying farms until returned in an advanced stage of pregnancy. The heifers during the first pregnancy were thus kept away from vibrio carriers until after the first calf was born. In June and July, 1919, 55 older cows, purchased and native, were placed on the young stock pasture. The three cases of abortion in heifers due to Vibrio fetus occurred October 24, November 9, and December 2, 1919. The age and condition of the fetuses accord very well with the assumption that Vibrio fetus was introduced among the young stock in June or July of the same year. The information gathered thus far concerning vibrionic abortion in this herd enables us to formulate a tentative hypothesis subject to modification with increasing knowledge of this type of infectious abortion. The infectious agent was probably introduced by purchased cows in 1917 or earlier. It gained a certain headway up to 1919, then the number of cases declined so that between May, 1919, and May, 1920, only the above three cases in heifers, and one case of mixed infection with Bacillus abortus in an older cow, were detected. During the same period cases due to Bacillus abortus continued undiminished. The greater resistance of Bacillus abortus manifested in cultures as compared with Vibrio fetus is thus reflected in its behavior in nature. The temporary dying out of the infection indicates that natural immunization of a herd to Vibrio fetus proceeds quite rapidly. Another outbreak may be expected when the immunity of the herd has declined in the absence of the infecting agent and the latter is reintroduced from without, or it may reappear at any time when a vibrio of higher virulence is brought in.     

AN OUTBREAK OF PNEUMONIA IN DAIRY COWS ATTRIBUTED TO BACILLUS BOVISEPTICUS

All outbreak of pneumonia in dairy cows attributed to Bacillus bovisepticus is described. About twenty cows and two calves were affected. The first cases were noted in cows purchased in Michigan. The disease next appeared in another lot of cows from Pennsylvania and subsequently attacked native stock. Of the ten cases which came under our observation, five apparently recovered, two died, and two severely affected cows were killed. The other case developed multiple abscesses of the lung and was finally killed. The more characteristic symptoms observed were high temperature, rapid respiration, dyspnea, cough, dullness on percussion, bronchial breathing, and albuminuria. The pneumonia was diffuse but first affected the cephalic and more dependent lobes. The process varied from hyperemia and hemorrhage to exudation of fibrin and leucocytes within the air spaces. The plugging of the interlobular lymph channels and blood vessels with fibrin was frequent. Bacillus bovisepticus was isolated in pure cultures from all involved portions of lung at autopsy. It was not found in blood cultures during the height of the disease, nor could it be obtained from the spleen and kidney after death.     

THE PATHOLOGICAL CHANGES IN THE TESTES IN EPIDEMIC PNEUMONIA

The testicular changes in pneumonia are without clinical manifestations, are non-specific, focal in character, independent of the infecting organisms or the antecedent disease, and vary in severity directly with the total length of the illness. The process is a continuous one, divisible into stages in which the following features are recognizable: (1) cessation of spermatogenesis; (2) degeneration of preformed spermatocytes, spermatids, and spermatozoa; (3) desquamation of altered cells and fragments of the same; (4) formation of giant cells in the tubule walls with subsequent liberation into the lumen; (5) disappearance of all desquamated cells and all those derived from the spermatogonia by mitosis; (6) in some instances thickening of the hyaline layer of the basement membrane. Older lesions are frequently found which continue the structural alteration of the tubules by hyalinosis and destruction of cells until they ultimately disappear. These lesions are not believed to be connected with the present illness. Edema may represent the acute injury in another form, and round cell infiltration suggests that possibly other factors than toxins may have a part in the tissue alterations. In the absence of definite evidence to the contrary, the cause is assumed to be circulating toxins, as Wolbach (12) claims for influenzal cases. The hemolytic streptococcus produced more extensive changes, both epithelial and interstitial, in primary pneumonia occurring during the measles epidemic than when pneumonia followed as a secondary infection; in the latter cases the pulmonary complications covered a relatively shorter period. Measles and epidemic influenza had little apparent effect upon the testes, except that the former caused mild inhibition of spermatogenesis; evidence regarding the latter is inconclusive. The Pfeiffer bacillus was always associated with other organisms, in primary infections and in those following measles. It occurred alone in a few cases after epidemic influenza, but the testicular lesion was not distinctive. The pneumococcus when alone in primary infections or after an epidemic disease produced a uniformly mild picture which was not intensified when associated with the influenza bacillus. Giant cells were much more frequent after influenzal pneumonia regardless of its cause and were associated with large numbers of other desquamated cells. They are formed in the walls of tubules by futile mitotic effort and incomplete protoplasmic separation, the abnormality of the process being further suggested by the early severing of cytoplasmic attachments and rapid desquamation. The series is unique in its uniformity, in the care exercised in the bacteriological examinations, and in the relative freedom from complicating factors.     

The microvasculature of the synovial membrane of the monkey: Ultrastructural studies

The normal synovial microvasculature of Cebus albifrons monkeys is characterized by fenestrated superficial capillaries and venules, and deeper vessels with thicker, active-appearing endothelium from which intravenously injected tracers occasionally were seen to have leaked. Carbon tracer was also identified in endothelial phagosomes. The possible roles of these vessels in joint inflammation is discussed. Leakage of still unidentified pathogenic agents from synovial vessels may be an early event in joint inflammation.     

Utility of Diabetes Type–Specific Genetic Risk Scores for the Classification of Diabetes Type Among Multiethnic Youth

OBJECTIVEGenetic risk scores (GRS) aid classification of diabetes type in White European adult populations. We aimed to assess the utility of GRS in the classification of diabetes type among racially/ethnically diverse youth in the U.S.RESEARCH DESIGN AND METHODSWe generated type 1 diabetes (T1D)- and type 2 diabetes (T2D)-specific GRS in 2,045 individuals from the SEARCH for Diabetes in Youth study. We assessed the distribution of genetic risk stratified by diabetes autoantibody positive or negative (DAA^+/−) and insulin sensitivity (IS) or insulin resistance (IR) and self-reported race/ethnicity (White, Black, Hispanic, and other).RESULTST1D and T2D GRS were strong independent predictors of etiologic type. The T1D GRS was highest in the DAA⁺/IS group and lowest in the DAA⁻/IR group, with the inverse relationship observed with the T2D GRS. Discrimination was similar across all racial/ethnic groups but showed differences in score distribution. Clustering by combined genetic risk showed DAA⁺/IR and DAA⁻/IS individuals had a greater probability of T1D than T2D. In DAA⁻ individuals, genetic probability of T1D identified individuals most likely to progress to absolute insulin deficiency.CONCLUSIONSDiabetes type–specific GRS are consistent predictors of diabetes type across racial/ethnic groups in a U.S. youth cohort, but future work needs to account for differences in GRS distribution by ancestry. T1D and T2D GRS may have particular utility for classification of DAA⁻ children.     

Animal soundscapes reveal key markers of Amazon forest degradation from fire and logging

Safeguarding tropical forest biodiversity requires solutions for monitoring ecosystem structure over time. In the Amazon, logging and fire reduce forest carbon stocks and alter habitat, but the long-term consequences for wildlife remain unclear, especially for lesser-known taxa. Here, we combined multiday acoustic surveys, airborne lidar, and satellite time series covering logged and burned forests (n = 39) in the southern Brazilian Amazon to identify acoustic markers of forest degradation. Our findings contradict expectations from the Acoustic Niche Hypothesis that animal communities in more degraded habitats occupy fewer “acoustic niches” defined by time and frequency. Instead, we found that aboveground biomass was not a consistent proxy for acoustic biodiversity due to the divergent patterns of “acoustic space occupancy” between logged and burned forests. Ecosystem soundscapes highlighted a stark, and sustained reorganization in acoustic community assembly after multiple fires; animal communication networks were quieter, more homogenous, and less acoustically integrated in forests burned multiple times than in logged or once-burned forests. These findings demonstrate strong biodiversity cobenefits from protecting burned Amazon forests from recurrent fire. By contrast, soundscape changes after logging were subtle and more consistent with acoustic community recovery than reassembly. In both logged and burned forests, insects were the dominant acoustic markers of degradation, particularly during midday and nighttime hours, which are not typically sampled by traditional biodiversity field surveys. The acoustic fingerprints of degradation history were conserved across replicate recording locations, indicating that soundscapes may offer a robust, taxonomically inclusive solution for digitally tracking changes in acoustic community composition over time.

Biological diversity is disappearing rapidly in response to human activity, especially in tropical forests, which are home to well over half of Earth’s terrestrial species (1). Global concern over greenhouse gas emissions from tropical forests (2) has led to international efforts to Reduce Emissions from Deforestation and Forest Degradation (REDD+) (3). Retention of diverse ecosystems supports climate change mitigation and adaptation (4); yet, carbon-focused conservation may not result in a commensurate win for tropical forest biodiversity (5). Longstanding data gaps on species distributions and uncertainty regarding the direct and indirect impacts of human activity on biodiversity complicate efforts to quantify the interplay between carbon and biodiversity (6, 7).Across the tropics, the Brazilian Amazon has the highest rates of deforestation (8), and forest degradation from fire and logging may double biodiversity loss from deforestation alone (9). However, the long-term impacts of human activity on Amazon biodiversity remain highly uncertain due, in part, to the spatial heterogeneity among degraded forests from differences in the timing, frequency, extent, and severity of disturbances (10). Time-varying heterogeneity in the biodiversity of degraded forests may also explain some of the apparent contradictions in previous studies of degradation impacts on birds, the most well-studied Amazonian taxa. Many nectarivorous birds, for example, increase in abundance immediately after logging but ultimately decline. Yet, many insectivorous birds show immediate sensitivity to changes in habitat from logging but continue to decline in abundance over time (11). Time dependence also complicates efforts to measure the effects of degradation on insects, a problem confounded by limited research (12).Addressing the tropical biodiversity extinction crisis, therefore, requires an efficient, distributed, long-term monitoring system to assess ecosystem structure (13). Traditional, ground-based biodiversity inventories are logistically prohibitive to conduct at scale, and limited taxonomic expertise perpetuates large data discrepancies for lesser-known taxa, such as insects, which constitute the bulk of tropical biodiversity (7). Advances in the emerging discipline of acoustic remote sensing, or ecoacoustics, may permit large-scale biodiversity monitoring for multiple taxa, including unidentifiable species, based on the aggregate sound signature of the animal community, or soundscape (14–16). Since multiple sites can be recorded simultaneously over time, sound surveys reduce the effort and cost associated with routine monitoring and facilitate standardized assessments of community variation and ecosystem recovery. Most previous efforts to utilize acoustic data for biodiversity monitoring have focused on detecting known vocalizations associated with individual species (17, 18), but there is increasing interest in evaluating the entire collection of signals in a given soundscape to derive measures of ecosystem intactness that include all sound-generating taxa without definitive species identification (15, 16, 19, 20).The Acoustic Niche Hypothesis (ANH) (21) is a core premise of ecoacoustics and the prevailing organizing principle for assessing diversity (16), community similarity (22), and human impacts (23, 24) using soundscape data. The ANH posits that more intact habitats support more biodiverse communities that occupy more “acoustic niches.” Greater niche partitioning of available acoustic space, defined by frequency and time of day, is posited to minimize communication interference among coexisting species. The ANH implies a positive linear relationship between habitat intactness (i.e., biomass) and acoustic niche infilling or acoustic space occupancy (ASO) by the “animal orchestra.” The corollary is that more degraded habitats support less acoustic infilling due to vacant acoustic niches from local species extirpations (25). Ecoacoustic approaches have great potential to extend monitoring capabilities in the hyperdiverse tropics, where competition for acoustic space is strongest (16, 26). Still, large uncertainties remain as to whether soundscape infilling can be used as a robust proxy for ecosystem intactness to monitor landscapes altered by human activity (27).Here, we test the ANH across logged and burned Amazon forests to identify acoustic markers of forest degradation (Fig. 1). We collected coincident high-density airborne lidar data and multiday acoustic recordings (214 24-h surveys) during September and October 2016 in 39 forests with different times since logging (4 to 23 y) and histories of fire activity (1 to 5 fires), stratified based on a 33-y time series of annual Landsat imagery (10). We used space-for-time substitution and two complementary analytic approaches to characterize threshold effects and time dependence for changes in the structure of animal soundscapes along gradients of degradation history (see Materials and Methods). First, we calculated ASO for each site at hourly and 1-min time steps to test the ANH and to quantify the magnitude, persistence, and variability in the infilling of acoustic space following forest degradation. Second, we developed a network-based approach to capture additional complexity from the soundscape data to track the composition and co-occurrences of “acoustic pseudotaxa” (defined as the community components that occupy the same acoustic niche) along degradation and recovery pathways. Our findings demonstrate that soundscapes encode digital markers of the history of degradation from human activity, revealing distinct patterns of community change following logging and fire. This study paves the way for more widespread use of ecoacoustics to benchmark and monitor changes in acoustic community composition in human-altered tropical forest landscapes, especially in remote regions with many unknown species.Open in a separate windowFig. 1.Acoustic recording sites in logged and burned forests (n = 39) were distributed across 9,400 km² in northern Mato Grosso, Brazil (Upper Left). Colored boxes identify subsets of the study domain to illustrate how the triplicate sampling scheme was designed to capture the heterogeneity in habitat structure and acoustic community composition in logged (yellow) and burned (black) forests. False-color composites of Landsat imagery (2014, 543-RGB) in each panel show deforested areas in magenta and gradients of forest cover in shades of green.