Up-regulation of WNT-4 signaling and dosage-sensitive sex reversal in humans

Wnt-4, a member of the Wnt family of locally acting secreted growth factors, is the first signaling molecule shown to influence the sex-determination cascade. In mice, a targeted deletion of Wnt-4 causes the masculinization of XX pups. Therefore, WNT-4, the human homologue of murine Wnt-4, is a strong candidate gene for sex-reversal phenotypes in humans. In this article, we show that, in testicular Sertoli and Leydig cells, Wnt-4 up-regulates Dax1, a gene known to antagonize the testis-determining factor, Sry. Furthermore, we elucidate a possible mechanism for human XY sex reversal associated with a 1p31-p35 duplication including WNT-4. Overexpression of WNT-4 leads to up-regulation of DAX1, which results in an XY female phenotype. Thus, WNT-4, a novel sex-determining gene, and DAX1 play a concerted role in both the control of female development and the prevention of testes formation. These observations suggest that mammalian sex determination is sensitive to dosage, at multiple steps in its pathway.     

Cytologic appearances in invasive lobular carcinoma of the breast. A study of 21 cases

OBJECTIVE: To examine the fine needle aspiration cytologic features of invasive lobular carcinoma of breast and to discuss problems that may occur in cytodiagnosis. STUDY DESIGN: Fine needle aspiration cytologic smears from 21 cases of invasive lobular carcinoma (ILC) of breast were subjected to detailed cytomorphologic analysis. Features studied included pattern of cells, size of cells, nuclear placement, pleomorphism, presence of intracytoplasmic lumina (ICL) and signet ring cells. RESULTS: Cellularity was generally moderate or high, and the pattern was predominantly or partly dissociated in 86% of cases. Rosettelike pattern was discerned in alveolar-type ILC. Cell size was usually small or intermediate, with nuclei placed eccentrically in most cases. ICLs with or without signet ring cells were present in 12 cases (57%). CONCLUSION: A cytologic picture consisting of predominantly dissociated small or intermediate-sized tumor cells with eccentric nuclei, with some of the cells showing ICLs, is highly suggestive of ILC. Indian file pattern, another characteristic feature of ILC, is, however, focal and inconsistent. Variant patterns of ILC may show other cytologic features, such as rosettelike pattern (alveolar variant of ILC) or large cell pattern (pleomorphic variant of ILC) and may consequently be difficult to categorize on cytologic smears.     

Goat serum as an alternative to establish cell culture from Indian major carp, Cirrhinus mrigala

Serum from goat, calf, and chicken sources were evaluated in terms of attachment, growth, and proliferation of explants of Indian major carp, Cirrhinus mrigala. The attachment of explants viz. heart, liver, and kidney was directly proportional to the concentration of the serum. Among these sera, the highest percentage of attachment, growth, and proliferation was recorded for 10% goat serum and 15% newborn calf serum without affecting their cell morphology. On contrary to these sera, chicken serum at 15% concentration was found to be mildly toxic for all the explants. The cell count was significantly high for the kidney, liver, and heart at 10% goat serum among all the tested sera as well as concentration. Similarly, the liver, heart, and kidney explants were found to survive up to the tenth, seventh, and ninth passage, respectively. Therefore, the goat serum at 10% concentration can be used as effectively as newborn calf serum for routine culture of fish cells.     

Distribution of energy reserves in a viviparous skink: Does tail autotomy involve the loss of lipid stores?

Abstract Caudal autotomy is an effective defensive strategy used by many lizards to facilitate escape during predatory encounters. However, it has several potentially severe consequences, including a range of energetic costs that are believed to result from the depletion of caudal lipid reserves during tail loss. In this study we examined the possible effect of caudal autotomy on the energetic reserves of a small viviparous skink, Niveoscincus metallicus (O'Shaughnessy 1874). Animals of each sex were collected on three occasions to assess the distribution of lipid stores. In addition, the frequency and position of naturally occurring tail breaks were determined. Both abdominal and caudal lipid stores are present in N. metallicus; however, caudal fat bodies comprise the majority (55–78%) of these fat reserves. Temporal variation in fat body mass, both abdominal and caudal, was evident. There was a significant relationship between the two fat stores, which was distorted in pregnant females, when relatively more fat was stored in the tail. Examination of the distribution of caudal fat in the tail revealed that the majority (90–95%) occurs within the proximal third of the tail. The remainder is located in the middle portion of the tail, with no reserves in the most distal tail section. During late pregnancy, females store relatively more fat closer to the body. The frequency of tail loss in a natural population of N. metallicus was extremely high (78%). Tail breaks were normally distributed along the length of the tail (i.e. most near the middle and fewer distal and proximal breaks). Thus there was a relatively high chance of some lipid depletion as a result of tail loss, but because 76% of breaks occur in the middle and distal thirds of the tail, there is a high probability that tail loss results in only minimal (i.e. <10%) lipid depletion. This is the first instance where both the energetic ‘value’ of the tail and the likelihood of lipid depletion during tail loss have been determined in a lizard. Overall, the combination of the aggregation of caudal fat reserves and position of naturally occurring tail breaks may enable N. metallicus to combine caudal fat storage and tail autotomy with minimal conflict.     

Primary Care Physicians’ Attitudes about Obesity and Its Treatment

Objective: This study was designed to assess physicians’ attitudes toward obese patients and the causes and treatment of obesity. Research Methods and Procedures: A questionnaire assessed attitudes in 2 geographically representative national random samples of 5000 primary care physicians. In one sample (N = 2500), obesity was defined as a BMI of 30 to 40 kg/m², and in the other (N = 2500), obesity was defined as a BMI > 40. Results: Six hundred twenty physicians responded. They rated physical inactivity as significantly more important than any other cause of obesity (p < 0.0009). Two other behavioral factors—overeating and a high‐fat diet—received the next highest mean ratings. More than 50% of physicians viewed obese patients as awkward, unattractive, ugly, and noncompliant. The treatment of obesity was rated as significantly less effective (p < 0.001) than therapies for 9 of 10 chronic conditions. Most respondents (75%), however, agreed with the consensus recommendations that a 10% reduction in weight is sufficient to improve obesity‐related health complications and viewed a 14% weight loss (i.e., 78 ± 5 kg from an initial weight of 91 kg) as an acceptable treatment outcome. More than one‐half (54%) would spend more time working on weight management issues if their time was reimbursed appropriately. Discussion: Primary care physicians view obesity as largely a behavioral problem and share our broader society's negative stereotypes about the personal attributes of obese persons. Practitioners are realistic about treatment outcomes but view obesity treatment as less effective than treatment of most other chronic conditions.     

Evaluation of habitat suitability index models by global sensitivity and uncertainty analyses: a case study for submerged aquatic vegetation

Habitat suitability index (HSI) models are commonly used to predict habitat quality and species distributions and are used to develop biological surveys, assess reserve and management priorities, and anticipate possible change under different management or climate change scenarios. Important management decisions may be based on model results, often without a clear understanding of the level of uncertainty associated with model outputs. We present an integrated methodology to assess the propagation of uncertainty from both inputs and structure of the HSI models on model outputs (uncertainty analysis: UA) and relative importance of uncertain model inputs and their interactions on the model output uncertainty (global sensitivity analysis: GSA). We illustrate the GSA/UA framework using simulated hydrology input data from a hydrodynamic model representing sea level changes and HSI models for two species of submerged aquatic vegetation (SAV) in southwest Everglades National Park: Vallisneria americana (tape grass) and Halodule wrightii (shoal grass). We found considerable spatial variation in uncertainty for both species, but distributions of HSI scores still allowed discrimination of sites with good versus poor conditions. Ranking of input parameter sensitivities also varied spatially for both species, with high habitat quality sites showing higher sensitivity to different parameters than low‐quality sites. HSI models may be especially useful when species distribution data are unavailable, providing means of exploiting widely available environmental datasets to model past, current, and future habitat conditions. The GSA/UA approach provides a general method for better understanding HSI model dynamics, the spatial and temporal variation in uncertainties, and the parameters that contribute most to model uncertainty. Including an uncertainty and sensitivity analysis in modeling efforts as part of the decision‐making framework will result in better‐informed, more robust decisions.     

Pten Regulates Epithelial Cytodifferentiation during Prostate Development

Gene expression and functional studies have indicated that the molecular programmes involved in prostate development are also active in prostate cancer. PTEN has been implicated in human prostate cancer and is frequently mutated in this disease. Here, using the Nkx3.1:Cre mouse strain and a genetic deletion approach, we investigate the role of Pten specifically in the developing mouse prostate epithelia. In contrast to its role in other developing organs, this gene is dispensable for the initial developmental processes such as budding and branching. However, as cytodifferentiation progresses, abnormal luminal cells fill the ductal lumens together with augmented epithelial proliferation. This phenotype resembles the hyperplasia seen in postnatal Pten deletion models that develop neoplasia at later stages. Consistent with this, gene expression analysis showed a number of genes affected that are shared with Pten mutant prostate cancer models, including a decrease in androgen receptor regulated genes. In depth analysis of the phenotype of these mice during development revealed that loss of Pten leads to the precocious differentiation of epithelial cells towards a luminal cell fate. This study provides novel insight into the role of Pten in prostate development as part of the process of coordinating the differentiation and proliferation of cell types in time and space to form a functional organ.     

Sanitation,Stress, and Life Stage: A Systematic Data Collection Study among Women in Odisha,India

Emerging evidence demonstrates how inadequate access to water and sanitation is linked to psychosocial stress, especially among women, forcing them to navigate social and physical barriers during their daily sanitation routines. We examine sanitation-related psychosocial stress (SRPS) across women’s reproductive lives in three distinct geographic sites (urban slums, rural villages, and rural tribal villages) in Odisha, India. We explored daily sanitation practices of adolescent, newly married, pregnant, and established adult women (n = 60) and identified stressors encountered during sanitation. Responding to structured data collection methods, women ranked seven sanitation activities (defecation, urination, menstruation, bathing, post-defecation cleaning, carrying water, and changing clothes) based on stress (high to low) and level of freedom (associated with greatest freedom to having the most restrictions). Women then identified common stressors they encountered when practicing sanitation and sorted stressors in constrained piles based on frequency and severity of each issue. The constellation of factors influencing SRPS varies by life stage and location. Overall, sanitation behaviors that were most restricted (i.e., menstruation) were the most stressful. Women in different sites encountered different stressors, and the level of perceived severity varied based on site and life stage. Understanding the influence of place and life stage on SRPS provides a nuanced understanding of sanitation, and may help identify areas for intervention.