Fishes show one of the widest ranges of sperm competition intensity of any animal group. Here we present a comparative study whose aim is to investigate the effect of relative intensity of sperm competition on investment in spermatogenesis and the number and size of sperm produced. We find that both the gonadosomatic index (GSI = [gonad weight/body weight] x 100) and sperm numbers increase with intensity of sperm competition across species but that sperm length decreases. These new findings are consistent with a raffle-based mode of sperm competition in fishes. Most of these results (positive correlation of the GSI and sperm number with sperm competition intensity) concur with the predictions of current sperm competition theory. However, we also find that sperm longevity decreases with sperm length across species. Current models for continuous fertilization suggest that if length increases a sperm's speed but decreases its longevity, sperm length should increase with sperm competition intensity, whereas models for instant fertilization suggest that sperm length should remain constant. The negative relationship found between sperm competition and sperm length therefore does not fit predictions of either model.

The objective of this study was to evaluate the pathology time course of the LRRK2 knockout rat model of Parkinson’s disease at 1-, 2-, 4-, 8-, 12-, and 16-months of age. The evaluation consisted of histopathology and ultrastructure examination of selected organs, including the kidneys, lungs, spleen, heart, and liver, as well as hematology, serum, and urine analysis. The LRRK2 knockout rat, starting at 2-months of age, displayed abnormal kidney staining patterns and/or morphologic changes that were associated with higher serum phosphorous, creatinine, cholesterol, and sorbitol dehydrogenase, and lower serum sodium and chloride compared to the LRRK2 wild-type rat. Urinalysis indicated pronounced changes in LRRK2 knockout rats in urine specific gravity, total volume, urine potassium, creatinine, sodium, and chloride that started as early as 1- to 2-months of age. Electron microscopy of 16-month old LRRK2 knockout rats displayed an abnormal kidney, lung, and liver phenotype.  In contrast, there were equivocal or no differences in the heart and spleen of LRRK2 wild-type and knockout rats. These findings partially replicate data from a recent study in 4-month old LRRK2 knockout rats [1] and expand the analysis to demonstrate that the renal and possibly lung and liver abnormalities progress with age. The characterization of LRRK2 knockout rats may prove to be extremely valuable in understanding potential safety liabilities of LRRK2 kinase inhibitor therapeutics for treating Parkinson’s disease.

The liver has a number of important functions in innate and adaptive immunity. Contributions to the innate (nonspecific) immune system include production of acute phase proteins, nonspecific phagocytosis of particles, nonspecific pinocytosis of molecules, and nonspecific cell killing. Hepatic involvement in innate immunity contributes to the systemic response to local inflammation, clearance of particles and soluble molecules from the circulation, and killing of invading cells such as neoplastic cells. Liver involvement in the adaptive (specific) immune system includes deletion of activated T cells, induction of tolerance to ingested and self-antigens, extrathymic proliferation of T cells, and deletion of many of the signaling and effector molecules. Hepatic involvement in adaptive immunity allows clearance of activated T cells and signaling molecules following inflammatory reactions, and promotes immunologic tolerance toward potentially antigenic proteins that are absorbed from the intestinal tract. The liver is a major site of extrathymic T cell development, which assumes increasing significance with aging in mammals. Perturbations in hepatic structure or function can result in significant ramifications in both the innate and adaptive immune systems.

Charts and slides of 47 patients with primary retroperitoneal sarcomas (excluding pediatric rhabdomyosarcoma) were reviewed to determine clinical presentation, histologic features, extent of surgical resection, operative morbidity and mortality, use of radiation and/or chemotherapy, and survival data. Most patients presented with pain and a palpable mass. Leiomyosarcomas and liposarcomas were the most common tumors. Eighteen of the 47 patients (38%) had complete tumor excision; 68% required resection of adjacent organs. Operative morbidity was 33% with no mortality. After complete resection, the disease-free 5-year survival was 50% and the overall survival was 70% at 5 years; 10-year disease-free survival was 25% with an overall 58% survival at 10 years. Eleven patients (61%) developed recurrent disease with a median interval of 5 years following complete excision. Six patients received adjuvant radiation and/or chemotherapy with four remaining disease-free from 46 to 61 months. Eighteen patients underwent partial excision of tumor and 11 patients underwent biopsy only; these groups had similar survival curves with only 4% alive at 5 years. Their operative morbidity was 18% and mortality was 7%; median time to clinical evidence of tumor progression was 12 months. Sixty per cent of these patients received therapeutic radiation and/or chemotherapy, but their survival was the same as those undergoing surgery alone. These data emphasize the importance of an aggressive surgical approach in the treatment of retroperitoneal sarcomas. Complete tumor resection and total excision of recurrences will allow many patients long-term survival.

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