A CURE Lab in Introductory Biology at a Regional Comprehensive University Negatively Impacts Student Success in the Associated Lecture Course Among Students from Groups Underrepresented in Science.

Course-based undergraduate research experiences (CUREs) have been proposed as a mechanism to democratize access to the benefits of apprentice-style scientific research to a broader diversity of students, promoting inclusivity and increasing student success and retention. As we evaluate CUREs, it is essential to explore their effectiveness within the environments of regional comprehensive universities and community colleges, because they are important access points for a wide variety of students. It is also important to address the potential influence of volunteer bias, where students can opt to enroll in either the CURE or a traditional lab, on the outcomes of CUREs. We evaluated a CURE at a regional comprehensive university under conditions both with and without volunteer bias. We find that nonvolunteer students report a lower sense of discovery and relevance of the CURE compared with students who volunteered for the course. Importantly, we also find that our replacement of the traditional lab class with a CURE resulted in lower scores on exams in the associated lecture course among students who are both BIPOC and Pell eligible. We call for additional research on the effects of CUREs at nonresearch-intensive institutions and without volunteer bias, to better understand the impact of these classes.

Revisiting nephrogenic systemic fibrosis in 6 kidney transplant recipients: a single-center experience.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a fibrotic disorder occurring in patients with renal dysfunction. Exposure to gadolinium (Gd)-based contrast agents (GBCAs) during renal impairment is associated with development of NSF. METHODS: A cross-referenced search of kidney transplantation and radiology databases at a single institution revealed the prevalence of NSF in the transplant population. Clinical records and skin biopsy specimens from 6 patients with kidney transplant given a diagnosis of NSF were reviewed to identify contributing factors. RESULTS: Between January 1999 and December 2006, NSF was diagnosed in 6 of 705 patients with kidney transplant (0.9%). Renal function was impaired in all patients. Of 33 patients with kidney transplant exposed to GBCAs, 5 (15.2%) developed NSF. Disease onset ranged from 7 days to 11 months after exposure to GBCAs. All 5 patients exposed to GBCAs who developed NSF were also treated with a beta-blocker and clinical improvement was observed with discontinuation. The sixth case NSF appeared unrelated to Gd, without a known exposure, and testing of tissue via mass spectrometry revealed no Gd. Symptoms of NSF in this patient disappeared after administration of darbepoetin was switched from subcutaneous to intravenous injection. One patient with NSF who manifested the highest Gd level in tissue died 22 months after disease onset. LIMITATIONS: The study represents the retrospective experience of only a single center. CONCLUSIONS: NSF can develop in kidney transplant recipients with altered graft function. In these patients, exposure to GBCAs appears associated with development of NSF. The role of beta-blockers in the course of the disease merits further investigation.

Significance of cell kinetic parameters in the prognosis of malignant melanoma: a review.

Malignant melanoma has been extensively studied concerning methods of predicting progression and clinical outcome. The maximum tumor thickness as measured by Breslow's method is the cornerstone prognostic criterion, but despite this, evolution of the disease in some patients remains unpredictable, confirming that new reliable prognostic factors are awaited. Cell kinetic evaluation has been shown to be a useful tool for assessing the prognosis of breast and gastrointestinal cancer patients. Indeed, in these fields, the mitotic index and MIB-1 expression index, which are indirect estimates of the growth fraction of tumor cell population, are commonly shown to correlate with tumor grade and patient survival and presented as prognostic factors. In melanoma, results of cell kinetic investigations are conflicting: some studies have established a link between high proliferative activity and a bad prognosis, whereas other reports suggest the opposite. The aim of this review is to discuss these findings.

Autophagy in development and stress responses of plants.

The uptake and degradation of cytoplasmic material by vacuolar autophagy in plants has been studied extensively by electron microscopy and shown to be involved in developmental processes such as vacuole formation, deposition of seed storage proteins and senescence, and in the response of plants to nutrient starvation and to pathogens. The isolation of genes required for autophagy in yeast has allowed the identification of many of the corresponding Arabidopsis genes based on sequence similarity. Knockout mutations in some of these Arabidopsis genes have revealed physiological roles for autophagy in nutrient recycling during nitrogen deficiency and in senescence. Recently, markers for monitoring autophagy in whole plants have been developed, opening the way for future studies to decipher the mechanisms and pathways of autophagy, and the function of these pathways in plant development and stress responses.

A new dendritic cell vaccine generated with interleukin-3 and interferon-beta induces CD8+ T cell responses against NA17-A2 tumor peptide in melanoma patients.

Dendritic cells derived from monocytes cultured in the presence of type I interferon were found to induce efficient T cell responses against tumor antigens in vitro. We vaccinated eight stage III or IV melanoma patients with dendritic cells generated with interferon-beta and interleukin-3, activated by poly I: C, and pulsed with the tumor-specific antigen NA17.A2. This dendritic cell vaccine was well-tolerated with only minor and transient flu-like symptoms and inflammatory reactions at the injection sites. In most patients, isotopic imaging documented dendritic cells (DC) migration from the intradermal injection site to the draining lymph nodes. Finally, mixed lymphocyte-peptide culture under limiting dilution conditions followed by tetramer labeling indicated that three out of eight patients mounted a CD8 T cell response against the NA17.A2 antigenic peptide. We conclude that DC generated in type I-IFN represent an interesting alternative to DC generated in IL-4 and GM-CSF for cancer immunotherapy.

Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate.

The aim of the present phase I/II study was to evaluate the safety, immune responses and clinical activity of a vaccine based on autologous dendritic cells (DC) loaded with an allogeneic tumor cell lysate in advanced melanoma patients. DC derived from monocytes were generated in serum-free medium containing GM-CSF and IL-13 according to Good Manufacturing Practices. Fifteen patients with metastatic melanoma (stage III or IV) received four subcutaneous, intradermal, and intranodal vaccinations of both DC loaded with tumor cell lysate and DC loaded with hepatitis B surface protein (HBs) and/or tetanus toxoid (TT). No grade 3 or 4 adverse events related to the vaccination were observed. Enhanced immunity to the allogeneic tumor cell lysate and to TAA-derived peptides were documented, as well as immune responses to HBs/TT antigens. Four out of nine patients who received the full treatment survived for more than 20 months. Two patients showed signs of clinical response and received 3 additional doses of vaccine: one patient showed regression of in-transit metastases leading to complete remission. Eighteen months later, the patient was still free of disease. The second patient experienced stabilization of lung metastases for approximately 10 months. Overall, our results show that vaccination with DC loaded with an allogeneic melanoma cell lysate was feasible in large-scale and well-tolerated in this group of advanced melanoma patients. Immune responses to tumor-related antigens documented in some treated patients support further investigations to optimize the vaccine formulation.

Demodicosis and rosacea: epidemiology and significance in daily dermatologic practice.

BACKGROUND: Demodicoses are thought to be rare, occurring mainly for patients with immunosuppression. OBJECTIVE: We sought to demonstrate the high frequency of demodicoses and the overlapping with papulopustular rosacea (PPR) . METHODS: We conducted a prospective epidemiologic study among 10 dermatologists. High Demodex density (Dd) was confirmed by standardized skin surface biopsy. RESULTS: In all, 4372 diagnoses, in which 115 were demodicoses, were collected among 3213 patients. Demodicosis was the 9th most frequent diagnosis (13th new). Each dermatologist observed an average of 2.4 demodicoses a week (1.2 new). The proportion of demodicoses varied greatly according to the dermatologist. The general status was good in 110 patients; only 3 had known immunodeficiency. The most frequent symptoms were follicular scales (71%) and telangiectasia (63%). The mean Dd was higher in pityriasis folliculorum (m = 61 D/cm 2 ) than in PPR (m = 36 D/cm 2 ; P = .04); 42 patients with PPR had a high Dd, 6 had a low Dd. CONCLUSION: Demodicoses are frequent and occur among patients who are immunocompetent. PPR with normal Dd are rare.

Expression of galectin-3 in primary and metastatic melanoma: immunohistochemical studies on human lesions and nude mice xenograft tumors.

Galectins are a large family of proteins which bind galactoside-containing glycans. Their role in cancer seems to be important since members of the family may mediate cell adhesion and modulate cell growth. Galectin-3 (Gal-3) is expressed in the nucleus, in the cytoplasm and on the cell surface, and can also be secreted into the extracellular matrix. A series of experimental and clinical data have been reported which indicate that Gal-3 may play a putative role in carcinogenesis, cancer progression and the process of metastasis. To study the possible correlation between Gal-3 expression and malignant potential in primary melanoma lesions, we conducted an immunohistochemical study with monoclonal anti-Gal-3 antibody in a series of primary and metastatic melanoma lesions as well as benign skin pigmented lesions. We also developed a xenograft melanoma model in nude mice with two melanoma cell lines (ATCC G-361 and ATCC HT-144) and assessed staining with the Gal-3 antibody in the xenografts and the metastases. The expression of anti-Gal-3 staining was determined semiquantitatively. The expression of Gal-3 was higher in thin primary melanoma lesions than in benign pigmented skin lesions or metastases and seemed to correlate inversely with the aggressiveness as estimated by the Breslow index which is recognized as the main prognostic factor in melanoma. We propose Gal-3 expression in melanoma as a diagnostic and/or a prognostic parameter and suggest that further studies of such a role for Gal-3 are warranted.

Engineering for drought avoidance: expression of maize NADP-malic enzyme in tobacco results in altered stomatal function.

Water is a principal limitation to agricultural production during drought and in arid regions of the world. Mechanisms that plants use to cope with drought can be grouped into two different strategies: drought tolerance and drought avoidance. Previous efforts toward engineering plants for improved performance during drought have focused on drought tolerance, the ability to adjust to dry conditions. This report addresses the engineering of a drought-avoidance phenotype, which allows for the conservation of water during plant growth. The majority of water lost from plants occurs through stomata. When stomata are open, potassium, chloride and/or malate are present at high concentrations in guard cells. The accumulation of large numbers of ions during stomatal opening increases the turgor pressure of the guard cells, which results in increased pore size. Expression of a single gene from maize, NADP-malic enzyme (ME), which converts malate and NADP to pyruvate, NADPH, and CO(2), resulted in altered stomatal behaviour and water relations in tobacco. The ME-transformed plants had decreased stomatal conductance and gained more fresh mass per unit water consumed than did the wild type, but they were similar to the wild type in their growth and rate of development. Providing chloride via the transpiration stream partially reversed the effects of ME expression on stomatal aperture size, which is consistent with the interpretation that expression of ME altered malate metabolism in guard cells. These results suggest a role for malic enzyme in the mechanism of stomatal closure, as well as a potential mechanism for genetically altering plant water use.

Kinetics of leaf temperature fluctuation affect isoprene emission from red oak (Quercus rubra) leaves.

Because the rate of isoprene (2-methyl-1,3-butadiene) emission from plants is highly temperature-dependent, we investigated natural fluctuations in leaf temperature and effects of rapid temperature change on isoprene emission of red oak (Quercus rubra L.) leaves at the top of the canopy at Harvard Forest. Throughout the day, leaves often reached temperatures as much as 15 degrees C above air temperature. The highest temperatures were reached for only a few seconds at a time. We compared isoprene emission rates measured when leaf temperature was changed rapidly with those measured when temperature was changed slowly. In all cases, isoprene emission rate increased with increasing leaf temperature up to about 32 degrees C and then decreased with higher temperatures. The temperature at which isoprene emission rates began to decrease depended on how quickly measurements were made. Isoprene emission rates peaked at 32.5 degrees C when measured hourly, whereas rates peaked at 39 degrees C when measurements were made every four minutes. This behavior reflected the rapid increase in isoprene emission rate that occurred immediately after an increase in leaf temperature, and the subsequent decrease in isoprene emission rate when leaf temperature was held steady for longer than 20 minutes. We concluded that the observed temperature response of isoprene emission rate is a function of measurement protocol. Omitting this parameter from isoprene emission models will not affect simulated isoprene emission rates at mild temperatures, but can increase isoprene emission rates at high temperatures.

Sex-specific physiology and source-sink relations in the dioecious plant Silene latifolia.

Differences in reproductive demands between the sexes of dioecious plants could cause divergence in physiology between the sexes. We found that the reproductive effort of female Silene latifolia plants increased to more than twice that of male plants or female plants that were prevented from setting fruit by lack of pollination after 4 weeks of flowering. Whole-plant source/sink ratios of pollinated females were significantly lower than those of males or unpollinated females because of investment in fruit. We hypothesized that these differences in source/sink ratio between the sexes and within females, depending on pollination, would lead to differences in leaf photosynthetic rates. Within females, we found that photosynthetic capacity was consistent with measurement of whole-plant source/sink ratio. Females that were setting fruit had 30% higher light-saturated photosynthetic rates by 28 days after flowering than females that were not setting fruit. Males, however, had consistently higher photosynthetic rates than females from 10 days after flowering onwards. Males also had approximately twice the dark respiration rates of fruiting females. We found that female reproductive structures are longer-lived and contribute more carbon to their own support than male reproductive structures. Despite the higher rates of leaf dark respiration and lower calyx photosynthetic rates, males fix more carbon than do females. We conclude that females have a sink-regulated mechanism of photosynthesis that allows them to respond to variations in fruit set. This mechanism is not, however, sufficient to explain why male S. latifolia plants have higher rates of photosynthesis, higher source/sink ratios, and lower reproductive allocation, but fail to grow larger than female plants.