Reconciliation in wild white-faced capuchins (Cebus capucinus)

The likelihood of reconciliation (defined as preferential peaceful contact among former opponents following conflicts) has been predicted to vary positively with relationship value and compatibility, and negatively with relationship security. Long-term data on wild white-faced capuchins (Cebus capucinus) indicate that dyads consisting of an adult female and an alpha male have high value and compatibility, but low security. Two studies of C. capucinus postconflict (PC) behavior were carried out at Lomas Barbudal Biological Reserve, Costa Rica. One study consisted of 30-min PC and matched control (MC) follows. The second study extracted PC and MC periods from long follows, yielding PC/MC periods averaging 105 min. In study 2, but not study 1, significantly more PC/MC pairs were attracted (former opponents affiliated with each other sooner in the PC period than in the MC period) than were dispersed (former opponents affiliated with each other sooner in the MC period than in the PC period). Reconciliation in study 2 could not be explained as a by-product of former opponents' tendency to seek affiliative contact with conspecifics generally, or of the spatial proximity of opponents following conflicts. Attempted reconciliation was less likely to be followed by renewed aggression when reconciliation attempts were delayed following conflicts. The data were insufficient for a formal test of differences in conciliatory tendency (the difference between the number of attracted and dispersed PC/MC pairs, divided by the total number of pairs) among dyad types to be conducted.     

Systemic lupus erythematosus

Imerslund-Gräsbeck syndrome (IGS) or selective vitamin B₁₂ (cobalamin) malabsorption with proteinuria is a rare autosomal recessive disorder characterized by vitamin B₁₂ deficiency commonly resulting in megaloblastic anemia, which is responsive to parenteral vitamin B₁₂ therapy and appears in childhood. Other manifestations include failure to thrive and grow, infections and neurological damage. Mild proteinuria (with no signs of kidney disease) is present in about half of the patients. Anatomical anomalies in the urinary tract were observed in some Norwegian patients. Vitamin B₁₂ absorption tests show low absorption, not corrected by administration of intrinsic factor. The symptoms appear from 4 months (not immediately after birth as in transcobalamin deficiency) up to several years after birth. The syndrome was first described in Finland and Norway where the prevalence is about 1:200,000. The cause is a defect in the receptor of the vitamin B₁₂-intrinsic factor complex of the ileal enterocyte. In most cases, the molecular basis of the selective malabsorption and proteinuria involves a mutation in one of two genes, cubilin (CUBN) on chromosome 10 or amnionless (AMN) on chromosome 14. Both proteins are components of the intestinal receptor for the vitamin B₁₂-intrinsic factor complex and the receptor mediating the tubular reabsorption of protein from the primary urine. Management includes life-long vitamin B₁₂ injections, and with this regimen, the patients stay healthy for decades. However, the proteinuria persists. In diagnosing this disease, it is important to be aware that cobalamin deficiency affects enterocyte function; therefore, all tests suggesting general and cobalamin malabsorption should be repeated after abolishment of the deficiency.     

Dietary patterns and changes in body weight in women

Objective: Our objective was to examine the association between adherence to dietary patterns and weight change in women. Research Methods and Procedures: Women (51,670, 26 to 46 years old) in the Nurses’ Health Study II were followed from 1991 to 1999. Dietary intake and body weight were ascertained in 1991, 1995, and 1999. A Western pattern, characterized by high intakes of red and processed meats, refined grains, sweets and desserts, and potatoes, and a prudent pattern, characterized by high intakes of fruits, vegetables, whole grains, fish, poultry, and salad dressing, were identified with principal component analysis, and associations between patterns and change in body weight were estimated. Results: Women who increased their Western pattern score had greater weight gain (multivariate adjusted means, 4.55 kg for 1991 to 1995 and 2.86 kg for 1995 to 1999) than women who decreased their Western pattern score (2.70 and 1.37 kg for the two time periods), adjusting for baseline lifestyle and dietary confounders and changes in confounders over time (p < 0.001 for both time periods). Furthermore, among women who increased their prudent pattern score, weight gain was smaller (multivariate‐adjusted means, 1.93 kg for 1991 to 1995 and 0.66 kg for 1995 to 1999) than among women who decreased their prudent pattern score (4.83 and 3.35 kg for the two time periods) (p < 0.001). The largest weight gain between 1991 and 1995 and between 1995 and 1999 was observed among women who decreased their prudent pattern score while increasing their Western pattern score (multivariate adjusted means, 6.80 and 4.99 kg), whereas it was smallest for the opposite change in patterns (0.87 and ?0.64 kg) (p < 0.001). Discussion: Adoption of a Western dietary pattern is associated with larger weight gain in women, whereas a prudent dietary pattern may facilitate weight maintenance.     

Glycosylation of PrPC Determines Timing of Neuroinvasion and Targeting in the Brain following Transmissible Spongiform Encephalopathy Infection by a Peripheral Route

Transmissible spongiform encephalopathy (TSE) infectivity naturally spreads from site of entry in the periphery to the central nervous system where pathological lesions are formed. Several routes and cells within the host have been identified as important for facilitating the infectious process. Expression of the glycoprotein cellular PrP (PrP^C) is considered a key factor for replication of infectivity in the central nervous system (CNS) and its transport to the brain, and it has been suggested that the infectious agent propagates from cell to cell via a domino-like effect. However, precisely how this is achieved and what involvement the different glycoforms of PrP have in these processes remain to be determined. To address this issue, we have used our unique models of gene-targeted transgenic mice expressing different glycosylated forms of PrP. Two TSE strains were inoculated intraperitoneally into these mice to assess the contribution of diglycosylated, monoglycosylated, and unglycosylated PrP in spreading of infectivity to the brain. This study demonstrates that glycosylation of host PrP has a profound effect in determining the outcome of disease. Lack of diglycosylated PrP slowed or prevented disease onset after peripheral challenge, suggesting an important role for fully glycosylated PrP in either the replication of the infectious agent in the periphery or its transport to the CNS. Moreover, mice expressing unglycosylated PrP did not develop clinical disease, and mice expressing monoglycosylated PrP showed strikingly different neuropathologic features compared to those expressing diglycosylated PrP. This demonstrates that targeting in the brain following peripheral inoculation is profoundly influenced by the glycosylation status of host PrP.Transmissible spongiform encephalopathies (TSE) or prion diseases are a group of fatal neurodegenerative diseases which include Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and goats, bovine spongiform encephalopathies (BSE) in cattle, and chronic wasting disease (CWD) in deer and elk (30). These diseases can be sporadic, familial, or acquired by infection, and the common hallmark is a distinct pathology in the central nervous system (CNS) characterized by neuronal loss, spongiform degeneration, and gliosis (38, 46).Expression of the host-encoded cellular PrP (PrP^C) is fundamental for the onset of disease since PrP-deficient mice are refractory to TSE infection (11, 31). PrP^C is a glycoprotein with two consensus sites for attachment of N-linked glycans (at codons 180 and 196 in the mouse) which are variably occupied, producing di-, mono-, and unglycosylated PrP (43). The diversity in glycosylation, combined with the complexity of added sugars, results in a large number of glycosylated forms of PrP (41). A central event associated with TSE infection is the conformational conversion of PrP^C into an abnormal protease-resistant form, PrP^Sc (39). PrP^Sc is deposited in brain and, in some but not all cases, in peripheral organs of individuals affected by TSE (21).Although the pathology associated with TSE is found in the brain, the periphery is the most natural route of acquiring infection. Evidence suggests that oral transmission via contaminated food is linked with transmission of BSE to humans, resulting in variant CJD (vCJD) (10, 47), and blood transfusion has been identified as a probable route of human-to-human transmission of vCJD (23, 27, 36). Moreover, parenteral administration of contaminated human tissue-derived therapeutics has been shown to facilitate iatrogenic spread of these diseases (8, 46). It is therefore important to understand the mechanisms that allow the infectious agent to propagate in the periphery and be transported to the CNS prior to the onset of neurodegeneration in the brain.Many studies have been conducted to understand routes of transmission (for a review see references 1 and 29). Lymphoid tissues such as the spleen have been shown to play a fundamental role in agent replication and propagation in the very early stages of disease. Indeed, studies of splenectomized and asplenic mice have shown the lymphoreticular system (LRS) to be an important site for TSE agent replication (14, 26). The periphery also appears to have a role in processing the infectious agent following intracerebral (i.c.) inoculation as PrP^Sc accumulates in the spleen shortly after inoculation and before accumulation of the abnormal protein in the brain (15, 17). Within the LRS, follicular dendritic cells (FDC) have been shown to be important for the uptake of infectivity and subsequent spreading toward the CNS (7, 28, 33, 35). Several studies have also suggested the peripheral nervous systems (PNS) as a potential route of infectivity to the brain, implicating the vagus and sciatic nerves in this process (5, 20, 25, 34).Expression of PrP^C in the peripheral tissues appears to be an important prerequisite for the transport of infectivity to the CNS following peripheral routes of inoculation. Indeed, it has been proposed that a continuous chain of cells expressing PrP^C is fundamental for TSE neuroinvasion (6, 40), with overexpression of endogenous PrP in the PNS greatly facilitating the spread of infectivity (19). Thus, host PrP appears to have a fundamental role in the uptake, transport, and replication of the infectious agent (6). Moreover, it has been suggested that the different PrP^C glycoforms may influence the timing of neuroinvasion by directly influencing the interaction with the infectious agent (19). However, the mechanism by which the different glycoforms are involved in these processes remains to be determined.In order to investigate the role of PrP^C glycosylation in TSE disease after peripheral infection with different TSE strains, we have used our inbred gene-targeted transgenic mice expressing different glycosylated forms of PrP. These mice expressed PrP with no sugars at the first (designated G1/G1 in homozygous mice) or the second glycosylation site (G2/G2) or both (G3/G3) under the control of the endogenous PrP promoter (13). We have previously shown that following intracerebral inoculation, all glycotypes are susceptible to infection with at least one TSE strain and that the type of PrP glycosylation in the host influenced the incubation period but not the distribution of pathological lesions in the brain (45). Here, we examine the influence of host PrP glycosylation on the peripheral acquisition of infection and demonstrate that, unlike the intracerebral route, mice without PrP glycosylation were resistant to disease and that the different glycoforms had a profound influence on not only the timing of disease but also the type and distribution of the PrP^Sc deposits in the brain.