SummaryIn multicellular organisms, telomerase is required to maintain telomere length in the germline but is dispensable in the soma. Mice, for example, express telomerase in somatic and germline tissues, while humans express telomerase almost exclusively in the germline. As a result, when telomeres of human somatic cells reach a critical length the cells enter irreversible growth arrest called replicative senescence. Replicative senescence is believed to be an anticancer mechanism that limits cell proliferation. The difference between mice and humans led to the hypothesis that repression of telomerase in somatic cells has evolved as a tumor-suppressor adaptation in large, long-lived organisms. We tested whether regulation of telomerase activity coevolves with lifespan and body mass using comparative analysis of 15 rodent species with highly diverse lifespans and body masses. Here we show that telomerase activity does not coevolve with lifespan but instead coevolves with body mass: larger rodents repress telomerase activity in somatic cells. These results suggest that large body mass presents a greater risk of cancer than long lifespan, and large animals evolve repression of telomerase activity to mitigate that risk.

In humans, adverse pregnancy outcomes (low birth weight, prematurity, and intrauterine growth retardation) are associated with exposure to urban air pollution. Experimental data have also shown that such exposure elicits adverse reproductive outcomes. We hypothesized that the effects of urban air pollution on pregnancy outcomes could be related to changes in functional morphology of the placenta. To test this, future dams were exposed during pregestational and gestational periods to filtered or nonfiltered air in exposure chambers. Placentas were collected from near-term pregnancies and prepared for microscopical examination. Fields of view on vertical uniform random tissue slices were analyzed using stereological methods. Volumes of placental compartments were estimated, and the labyrinth was analyzed further in terms of its maternal vascular spaces, fetal capillaries, trophoblast, and exchange surface areas. From these primary data, secondary quantities were derived: vessel calibers (expressed as diameters), trophoblast thickness (arithmetic mean), and total and mass-specific morphometric diffusive conductances for oxygen of the intervascular barrier. Two-way analysis of variance showed that both periods of exposure led to significantly smaller fetal weights. Pregestational exposure to nonfiltered air led to significant increases in fetal capillary surface area and in total and mass-specific conductances. However, the calibers of maternal blood spaces were reduced. Gestational exposure to nonfiltered air was associated with reduced volumes, calibers, and surface areas of maternal blood spaces and with greater fetal capillary surfaces and diffusive conductances. The findings indicate that urban air pollution affects placental functional morphology. Fetal weights are compromised despite attempts to improve diffusive transport across the placenta.

SummaryLarge, long-lived species experience more lifetime cell divisions and hence a greater risk of spontaneous tumor formation than smaller, short-lived species. Large, longlived species are thus expected to evolve more elaborate tumor suppressor systems. In previous work, we showed that telomerase activity coevolves with body mass, but not lifespan, in rodents: telomerase activity is repressed in the somatic tissues of large rodent species but remains active in small ones. Without telomerase activity, the telomeres of replicating cells become progressively shorter until, at some critical length, cells stop dividing. Our findings therefore suggested that repression of telomerase activity mitigates the increased risk of cancer in largerbodied species but not necessarily longer-lived ones. These findings imply that other tumor suppressor mechanisms must mitigate increased cancer risk in long-lived species. Here, we examined the proliferation of fibroblasts from 15 rodent species with diverse body sizes and lifespans. We show that, consistent with repressed telomerase activity, fibroblasts from large rodents undergo replicative senescence accompanied by telomere shortening and overexpression of p16 Ink4a and p21Cip1/Waf1 cycline-dependent kinase inhibitors. Interestingly, small rodents with different lifespans show a striking difference: cells from small shorter-lived species display continuous rapid proliferation, whereas cells from small long-lived species display continuous slow proliferation. We hypothesize that cells of small long-lived rodents, lacking replicative senescence, have evolved alternative tumor-suppressor mechanisms that prevent inappropriate cell division in vivo and slow cell growth in vitro . Thus, large-bodied species and small but long-lived species have evolved distinct tumor suppressor mechanisms.

The innervation of the capybara thoracic limb was characterized. The following nerves were observed constituting the right and left brachial plexus: n. dorsalis scapulae (C4 and C5; C4, C5 and C6) which innervates the m. serratus ventralis cervicis and m. rhomboideus; n. suprascapularis (C4, C5 and C6; C5, C6 and C7) supplying the m. supraspinatus and the m. infraspinatus; cranial and caudal nn. subscapulares (C5 and C6; C5, C6 and C7) innervating the m. subscapularis; n. axillaris (C5 and C6; C6, C7 and C8) which supplies the m. triceps brachii (caput mediale); n. radialis (C6, C7, C8 and T1; C6, C7 and C8) which innervates the m. triceps brachii (caput longum and caput mediale) and the m. extensor carpi radialis, m. extensor digitorum communis, m. extensor digitorum lateralis; n. medianus joined to the n. musculocutaneus (C6, C7, C8 and T1; C6, C7 and C8) supplying the m. biceps brachii, m. flexor carpi radialis and m. coracobrachialis; n. ulnaris (C6, C7, C8 and T1; C6, C7 and C8) leading to the m. flexor carpi radialis, the m. flexor carpi ulnaris and the m. flexor digitorum superficialis; n. thoracodorsalis (C6, C7, C8 and T1; C6, C7 and C8) supplying the m. latissimus dorsi; n. thoracicus lateralis (C8, T1; C7, C8, T1) which innervates m. pectoralis profundus (caudal portion); n. thoracicus longus (C6, C7; C7, C8) which is distributed to the m. serratus ventralis thoracis. A communication between the n. radialis and n. ulnaris was observed at the left brachial plexus.

The superior (cranial) cervical ganglion was investigated by light microscopy in adult rats, capybaras (Hydrochaeris hydrochaeris) and horses. The ganglia were vascularly perfused, embedded in resin and cut into semi-thin sections. An unbiased stereological procedure (disector method) was used to estimate ganglion neuron size, total number of ganglion neurons, neuronal density. The volume of the ganglion was 0.5 mm3 in rats, 226 mm3 in capybaras and 412 mm3 in horses. The total number of neurons per ganglion was 18,800, 1,520,000 and 3,390,000 and the number of neurons per cubic millimetre was 36,700, 7,000 and 8,250 in rats, capybaras and horses, respectively. The average neuronal size (area of the largest sectional profile of a neuron) was 358, 982 and 800 microm2, and the percentage of volume occupied by neurons was 33, 21 and 17% in rats, capybaras and horses, respectively. When comparing the three species (average body weight: 200 g, 40 kg and 200 kg), most of the neuronal quantitative parameters change in line with the variation of body weight. However, the average neuronal size in the capybara deviates from this pattern in being larger than that of in the horse. The rat presented great interindividual variability in all the neuronal parameters. From the data in the literature and our new findings in the capybara and horse, we conclude that some correlations exist between average size of neurons and body size and between total number of neurons and body size. However, these correlations are only approximate and are based on averaged parameters for large populations of neurons: they are less likely to be valid if one considers a single quantitative parameter. Several quantitative features of the nervous tissue have to be taken into account together, rather than individually, when evolutionary trends related to size are considered.

The purpose of this research was to study the mammary lymphatic drainage under a macroscopic and mesoscopic view, comparing the vascular pattern of healthy and neoplasic mammary glands injected with drawing ink alcoholic and fluorescein solutions, in 46 mongrel female dogs. The results pointed out that the thoracic gland is drained by the axillary lymph centre, but in mammary neoplasia either superficial cervical or ventral thoracic lymph centres can be involved. Cranial and caudal abdominal glands may be drained by the axillary, inguinofemoral and popliteal lymph centres. However, the popliteal drainage is specific for the healthy caudal abdominal mammary gland. The inguinal gland can be drained by both inguinofemoral and popliteal lymph centres in both neoplasic and healthy conditions. Regarding the mammary lymphatic communications, this research demonstrated that neoplasic glands present more types of anastomosis (40.9%), than healthy glands (33.33%), and an increase in contralateral anastomosis (50%) compared with healthy ones (33%). Given the data, the mammary neoplasia can change the lymphatic drainage pattern in terms of lymph centres and vascular arborization, thus forming new drainage channels and recruiting a larger number of lymph nodes. Lastly, some comments were made about the severity of a specific neoplasic mammary gland and conditions to be considered before making a decision in terms of the most adequate operative procedure, and suggestions for further investigations.

The total number of neurons in the superior cervical ganglion (SCG) of adult capybaras is known from a previous study, where a marked occurrence of binucleate neurons (13%) was also noted. Here, distribution, number and fate of binucleate neurons were examined in younger, developing capybaras, aged 3 months. The mean neuronal cross-sectional area was 575.2 microm2 for mononucleate neurons and 806.8 microm2 in binucleate neurons. Frequency of binucleate neurons was about 36%. The mean ganglion volume was about 190 mm3 in young capybaras and the mean neuronal density was about 9,517 neurons/mm3. The total number of neurons per ganglion was about 1.81 mill. Neuronal cell bodies constituted 22.5% of the ganglion volume and the average neuronal volume was 23,600 microm3. By comparing the present data with those previously published the conclusion is drawn that the maturation period was characterized by the following points: a 26% remarkable decrease in neuronal density which was significant (P < 0.05) and a significant 16% (P < 0.05) decrease in the total number of SCG neurons accompanied by a 23% decrease in the total number of SCG binucleate neurons.

Preparation of patient cadavers by intravascular injection of modified Larssen solution yielded suitable instructional models for surgical training.