Distribution of uterine histological changes in aged captive cheetahs (Acinonyx jubatus)

The histological effect on the felid uterus of sterilization, via ovariectomy or salpingectomy, is currently unknown. To investigate the association of ovariectomy or salpingectomy with uterine health, it is first necessary to establish if changes are distributed evenly throughout the uterus. Both laparoscopic ovariectomy and salpingectomy with concurrent sampling of the tip of the uterine horn are possible in the cheetah. Currently accepted practice for histopathological screening of the uterus utilizes four biopsy samples. It is not known whether this method accurately reflects the status of the entire uterus. In this study we histologically examined the uteri of six older cheetahs (one 7-year-old and five 10–10.5-year-old animals) via 21 tissue samples (three samples from seven different anatomical regions) per cheetah to determine overall uterine health. Although no defined lesions were detected, mild endometrial gland dilation, assumed to be of no functional consequence, was observed in multiple samples. The odds of observing this dilation was lowest in the uterine body and progressively increased in a cranial direction, being significantly higher at the tip of the uterine horns (OR = 11.5; 95% CI, 2.0-65.1; p = 0.006). This supported the reliability of sampling the tip of the uterine horn to screen for endometrial gland dilation.     

Scaling between macro- to microscale climatic data reveals strong phylogenetic inertia in niche evolution in plethodontid salamanders

Macroclimatic niches are indirect and potentially inadequate predictors of the realized environmental conditions that many species experience. Consequently, analyses of niche evolution based on macroclimatic data alone may incompletely represent the evolutionary dynamics of species niches. Yet, understanding how an organisms’ climatic (Grinnellian) niche responds to changing macroclimatic conditions is of vital importance for predicting their potential response to global change. In this study, we integrate microclimatic and macroclimatic data across 26 species of plethodontid salamanders to portray the relationship between microclimatic niche evolution in response to changing macroclimate. We demonstrate stronger phylogenetic signal in microclimatic niche variables than at the macroclimatic scale. Even so, we find that the microclimatic niche tracks climatic changes at the macroscale, but with a phylogenetic lag at million-year timescales. We hypothesize that behavioral tracking of the microclimatic niche over space and phenology generates the lag: salamanders preferentially select microclimates similar to their ancestral conditions rather than adapting with changes in physiology. We demonstrate that macroclimatic variables are weak predictors of niche evolution and that incorporating spatial scale into analyses of niche evolution is critical for predicting responses to climate change.     

Effects of reduced seawater pH on fertilisation, embryogenesis and larval development in the Antarctic seastar Odontaster validus

The effects of ocean acidification will be pronounced in high-latitude marine communities, although little is known on how reproduction in free-spawning polar invertebrates will respond. Using the circum-Antarctic sea star Odontaster validus, we examined fertilisation, larval survival and development under a controlled seawater treatment (temperature = ?0.5 °C, pH 8.1, pCO₂(aq) = 326.6 μatm, TA = 2,274.2 μmol kg soln^?1), two near-future pH treatments (pH 7.8 and 7.6) and an extreme treatment (pH 7.0). At a sperm concentration of 3.5 × 10⁵ sperm ml^?1, percentage of fertilisation was 98–90 % across a pH 8.1–7.0 range. At near-future pH ranges (pH 7.8 and 7.6), fertilisation was not significantly lower than in the control pH 8.1 except at the lowest sperm concentration (2.2 × 10³ sperm ml^?1) where fertilisation was reduced to 60 and 61 % in pH 7.6 and 7.8, respectively. Larval survival was not significantly affected by a decrease in pH of 0.3 units, but at pH 7.6 survival was significantly reduced. This difference was apparent at 9 days, and at the end of the experiment at 58 days, survival was 55 % compared with 85 % in the ambient treatment. Near-future changes to pH yielded smaller larvae, a result of both subtle differences in their morphology and slowed development rates, while larvae at pH 7.0 showed evidence of abnormal development. O. validus fertilisation and larval success declines in seawater pH conditions expected in coastal Antarctica over the coming decades, although the responses observed are within the range observed in warmer-water echinoderms.     

Short reviews

Milton M. Gordon, HUMAN NATURE, CLASS AND ETHNICITY. London and New York, Oxford University Press, 1978, 302 pp., £6.50, $11.95 ($3.50 paper).

June Teufel Dreyer, CHINA'S FORTY MILLIONS: MINORITY NATIONALITIES AND NATIONAL INTEGRATION IN THE PEOPLE'S REPUBLIC OF CHINA. Cambridge (Mass.) and London, Harvard University Press, 1976, 333 pp., £9.55.

W. Stanford Reid (ed), THE SCOTTISH TRADITION IN CANADA. Toronto, McClelland & Stewart, 1976, xi + 324 pp., $12.55.

I. H. Kawharu, MAORI LAND TENURE: STUDIES OF A CHANGING INSTITUTION. Oxford, Clarendon Press, 1977, 362 pp., £13.50.

David T. Wellman, PORTRAITS OF WHITE RACISM. London, Cambridge University Press, 1977, 254 pp., £9.50 (£4.00 paper).

Lucy Mair, AFRICAN KINGDOMS. Oxford, Clarendon Press, 1977, 151 pp., £3.95, (£1.95 paper).

Roger Scott, NORTHERN IRELAND: THE POLITICS OF VIOLENCE. Canberra Series in Administrative Studies 2., Canberra College of Advanced Education, 1977, 84 pp., n.p.

James A. Geschwender, CLASS, RACE AND WORKER INSURGENCY: THE LEAGUE OF BLACK REVOLUTIONARY WORKERS. London, Cambridge University Press, 1977, 249 pp., £8.50 (£3.50 paper).

Crawford Young, THE POLITICS OF CULTURAL PLURALISM. Madison, University of Wisconsin Press, 1976. 560 pp., £13.60.

D. C. R. A. Goonetilleke, DEVELOPING COUNTRIES IN BRITISH FICTION. London, Macmillan, 1977, 282 pp., £8.95.

M. M. Mahood, THE COLONIAL ENCOUNTER. London, Rex Collings, 1977, 210 pp., £4.75.

Brian V. Street, THE SAVAGE IN LITERATURE. London, Routledge & Kegan Paul, 1975, 207 pp., £5.75.     

Highly Divergent T-cell Receptor Binding Modes Underlie Specific Recognition of a Bulged Viral Peptide bound to a Human Leukocyte Antigen Class I Molecule

Human leukocyte antigen (HLA)-I molecules can present long peptides, yet the mechanisms by which T-cell receptors (TCRs) recognize featured pHLA-I landscapes are unclear. We compared the binding modes of three distinct human TCRs, CA5, SB27, and SB47, complexed with a “super-bulged” viral peptide (LPEPLPQGQLTAY) restricted by HLA-B*35:08. The CA5 and SB27 TCRs engaged HLA-B*35:08^LPEP similarly, straddling the central region of the peptide but making limited contacts with HLA-B*35:08. Remarkably, the CA5 TCR did not contact the α1-helix of HLA-B*35:08. Differences in the CDR3β loop between the CA5 and SB27 TCRs caused altered fine specificities. Surprisingly, the SB47 TCR engaged HLA-B*35:08^LPEP using a completely distinct binding mechanism, namely “bypassing” the bulged peptide and making extensive contacts with the extreme N-terminal end of HLA-B*35:08. This docking footprint included HLA-I residues not observed previously as TCR contact sites. The three TCRs exhibited differing patterns of alloreactivity toward closely related or distinct HLA-I allotypes. Thus, the human T-cell repertoire comprises a range of TCRs that can interact with “bulged” pHLA-I epitopes using unpredictable strategies, including the adoption of atypical footprints on the MHC-I.     

Oligarchies in Amazonian tree communities: a ten‐year review

This paper revisits various hypotheses about oligarchic patterns in Amazonian tree communities put forward by Pitman et al. (2001) . Together, these hypotheses predict that most lowland sites in the Amazon are located within large patches of relatively homogeneous edaphic and other environmental conditions, where an oligarchy of common, frequent tree species accounts for a majority of trees. To assess the degree to which these hypotheses have been corroborated or refuted over the last ten years, we reviewed > 200 studies published since 2001. We found overwhelming support for the hypo thesis that large‐scale oligarchies of common and frequent species are a common feature of Amazonian tree communities. At least 22 studies have documented oligarchies in Amazonian woody plant communities to date, and no studies have looked for oligarchies as defined by Pitman et al. (2001) and failed to find them. We argue that six publications that offer critiques of the oligarchy hypothesis do not constitute valid tests. The other hypotheses in Pitman et al. (2001) – one regarding the specific oligarchic taxa that dominate forests near the eastern base of the Andes and one that attempts to explain why oligarchic species exist – are less well supported by the literature, in large part because they have not been subjected to many tests. We discuss links between these hypotheses and other well‐known patterns and hypotheses in ecology (the abundance–occupancy relationship, the Janzen–Connell hypothesis, the niche‐environment hypothesis, and the niche breadth hypothesis), and provide additional detail to facilitate rigorous tests in the future. The paper concludes by presenting remote sensing evidence that large patches of relatively homogeneous environmental conditions account for most of the upland forest landscape across Amazonian Peru.     

Enzymatic Synthesis of s-Substituted l-Cysteines with Tryptophan Synthase of Escherichia coli

The α₂β₂ complex of tryptophan synthase from Escherichia coli catalyzes β-replacement reactions of l-serine and its derivatives (e.g., β-chloro-l-alanine and O-methyl-Dl-serine) with various alkanethiols. The products from thiobenzyl alcohol and ethanethiol were isolated to demonstrate the enzymatic synthesis of the corresponding S-substituted l-cysteines. Reactivities of various S-substituent donors were examined, and thiols such as thiobenzyl alcohol, 1-propanethiol and 1-butanethiol were found to be much more efficient substituent donors than the physiological substrate, indole. In addition, tryptophan synthase catalyzes β-replacement reactions of l-threonine with thiols to form the corresponding S-substituted β-methylcysteines, which are also produced by β-addition reactions of l-vinylglycine with thiols. These enzymatic reactions facilitate the synthesis of various sulfur-containing amino acids.     

Sympathetic support of energy expenditure and sympathetic nervous system activity after gastric bypass surgery

Objective:

This study was designed to determine how gastric bypass affects the sympathetically‐mediated component of resting energy expenditure (REE) and muscle sympathetic nerve activity (MSNA).

Design and Methods:

We measured REE before and after beta‐blockade in seventeen female subjects approximately three years post‐gastric bypass surgery and in nineteen female obese individuals for comparison. We also measured MSNA in a subset of these subjects.

Results:

The gastric bypass subjects had no change in REE after systemic beta‐blockade, reflecting a lack of sympathetic support of REE, in contrast to obese subjects where REE was reduced by beta‐blockade by approximately 5% (P < 0.05). The gastric bypass subjects, while still overweight (BMI = 29.3 vs 38.0 kg·m^?2 for obese subjects, P < 0.05), also had significantly lower MSNA compared to obese subjects (10.9 ± 2.3 vs. 21.9 ± 4.1 bursts·min^?1, P < 0.05). The reasons for low MSNA and a lack of sympathetically mediated support of REE after gastric bypass are likely multifactorial and may be related to changes in insulin sensitivity, body composition, and leptin, among other factors.

Conclusions:

These findings may have important consequences for the maintenance of weight loss after gastric bypass. Longitudinal studies are needed to further explore the changes in sympathetic support of REE and if changes in MSNA or tissue responsiveness are related to the sympathetic support of REE.

     

Granzyme M has a critical role in providing innate immune protection in ulcerative colitis

Inflammatory bowel disease (IBD) is an immunoregulatory disorder, associated with a chronic and inappropriate mucosal immune response to commensal bacteria, underlying disease states such as ulcerative colitis (UC) and Crohn''s disease (CD) in humans. Granzyme M (GrzM) is a serine protease expressed by cytotoxic lymphocytes, in particular natural killer (NK) cells. Granzymes are thought to be involved in triggering cell death in eukaryotic target cells; however, some evidence supports their role in inflammation. The role of GrzM in the innate immune response to mucosal inflammation has never been examined. Here, we discover that patients with UC, unlike patients with CD, display high levels of GrzM mRNA expression in the inflamed colon. By taking advantage of well-established models of experimental UC, we revealed that GrzM-deficient mice have greater levels of inflammatory indicators during dextran sulfate sodium (DSS)-induced IBD, including increased weight loss, greater colon length reduction and more severe intestinal histopathology. The absence of GrzM expression also had effects on gut permeability, tissue cytokine/chemokine dynamics, and neutrophil infiltration during disease. These findings demonstrate, for the first time, that GrzM has a critical role during early stages of inflammation in UC, and that in its absence colonic inflammation is enhanced.Inflammatory bowel disease (IBD) is a gut-associated inflammatory disorder, which stems from a dysfunctional mucosal immune response to commensal bacteria.¹ As a multifactorial disease, IBD is the consequence of a complex interplay between environmental triggers, genetic susceptibility, and immunoregulatory defects, resulting in a pathogenesis that is still poorly understood.² These interactions result in the inability of an individual to control the normal inflammatory response to pathogens in the gut, leading to a chronic state of sustained and inappropriate inflammation. IBD underlies disease states such as ulcerative colitis (UC) and Crohn''s disease (CD), with symptoms including weight loss, abdominal pain, diarrhea, and rectal bleeding which often require intensive medical therapy and resective surgery.³ The pathogenesis of IBD, characterized by a defective mucosal immune response to microbial exposure in the gastrointestinal tract, is thought to be caused by a dysfunctional immune response to host microbiota, infection by specific pathogens, and/or a defective mucosal barrier to luminal pathogens.^{1, 2} IBD patients also have a high risk of developing colitis-associated colon cancer (CAC).⁴ Additionally, histological assessment of inflamed ileal and colonic segments from IBD patients typically shows increased infiltration of immune cells, particularly neutrophils, as well as crypt abscesses, mucin depletion, and ulcers—all correlating with the severity of small bowel and colonic tissue damage.⁵Cytotoxic pathways mediated by lymphocytes directly trigger cell death in target cells.⁶ These cytotoxic pathways are mediated by proteins such as perforin, which mediates pore formation in the target cell surface and allows granzyme (Grz)s to enter the intracellular compartment and induce cell death.⁷ To date, five different Grzs have been identified in humans (GrzA, GrzB, GrzH, GrzK, and GrzM), whereas mice express eleven Grzs (GrzA, GrzB, GrzC, GrzD, GrzE, GrzF, GrzG, GrzK, GrzL, GrzM, and GrzN).^{8, 9} Walch et al.¹⁰ recently demonstrated that Grzs (GrzA and GrzB) directly kill bacteria through granulysin-mediated delivery, suggesting that Grzs act as microbial modulating factors. Moreover, recently GrzA was shown to be increased in the colon biopsies of UC patients undergoing treatment with Etrolizumab, a monoclonal antibody targeting the β7 integrin subunit. Higher levels of GrzA could predict which patients were more likely to benefit from the therapy; however, the precise mechanism of action of GrzA in UC remains to be addressed.¹¹ GrzM was initially described as being constitutively expressed by natural killer (NK) cells,^{12, 13} and specifically associated with inflammation.¹⁴ This enzyme has been shown to preferentially cleave methionine and leucine residues in target cells, mediating direct, non-specific cell death.^{15, 16} More recently, GrzM was also shown to be an important mediator for the release of MIP-1α from NK cells, inducing NK cell and neutrophil recruitment during early microbial infection.¹⁷ We now observe that GrzM expression is increased in inflamed colon tissue samples from UC, but not CD patients. Further, GrzM-deficient (GrzM^−/−) mice are more sensitive to a mouse model of IBD and IBD-induced colorectal cancer (CRC). These findings demonstrate, for the first time, that GrzM has a critical role in mediating the early stages of the gut mucosal immune response.