System-, teacher-, and student-level interventions for improving participation in online learning at scale in high schools.

Many school systems across the globe turned to online education during the COVID-19 pandemic. This context differs significantly from the prepandemic situation in which massive open online courses attracted large numbers of voluntary learners who struggled with completion. Students who are provided online courses by their high schools also have their behavior determined by actions of their teachers and school system. We conducted experiments to improve participation in online learning before, during, and right after the COVID-19 outbreak, with 1,151 schools covering more than 45,000 students in their final years of high school in Ecuador. These experiments tested light-touch interventions at scale, motivated by behavioral science, and were carried out at three levels: that of the system, teacher, and student. We find the largest impacts come from intervening at the system level. A cheap, online learning management system for centralized monitoring increased participation by 0.21 SD and subject knowledge by 0.13 SD relative to decentralized management. Centralized management is particularly effective for underperforming schools. Teacher-level nudges in the form of benchmarking emails, encouragement messages, and administrative reminders did not improve student participation. There was no significant impact of encouragement messages to students, or in having them plan and team-up with peers. Small financial incentives in the form of lottery prizes for finishing lessons did increase study time, but was less cost-effective, and had no significant impact on knowledge. The results show the difficulty in incentivizing online learning at scale, and a key role for central monitoring.

Laser-induced breakdown spectroscopy determination of toxic metals in fresh fish.

A method based on laser induced breakdown spectroscopy (LIBS) for monitoring lead and copper accumulation in edible fish, particularly "tilapia del Nilo" (Oreochromis niloticus) is presented. The capability of this analytical method is compared with results obtained by atomic absorption spectrometry. Detection limits by LIBS are 25 parts per million (ppm) for Pb and 100 ppm for Cu, values that are below the maximum permissible levels of some international standards. Application of LIBS detection allows the development of portable instruments for contamination control of edible fish.

Modulation of Ca2+-currents by sequential and simultaneous activation of adenosine A1 and A 2A receptors in striatal projection neurons.

D(1)- and D(2)-types of dopamine receptors are located separately in direct and indirect pathway striatal projection neurons (dSPNs and iSPNs). In comparison, adenosine A(1)-type receptors are located in both neuron classes, and adenosine A(2A)-type receptors show a preferential expression in iSPNs. Due to their importance for neuronal excitability, Ca(2+)-currents have been used as final effectors to see the function of signaling cascades associated with different G protein-coupled receptors. For example, among many other actions, D(1)-type receptors increase, while D(2)-type receptors decrease neuronal excitability by either enhancing or reducing, respectively, CaV1 Ca(2+)-currents. These actions occur separately in dSPNs and iSPNs. In the case of purinergic signaling, the actions of A(1)- and A(2A)-receptors have not been compared observing their actions on Ca(2+)-channels of SPNs as final effectors. Our hypotheses are that modulation of Ca(2+)-currents by A(1)-receptors occurs in both dSPNs and iSPNs. In contrast, iSPNs would exhibit modulation by both A(1)- and A2A-receptors. We demonstrate that A(1)-type receptors reduced Ca(2+)-currents in all SPNs tested. However, A(2A)-type receptors enhanced Ca(2+)-currents only in half tested neurons. Intriguingly, to observe the actions of A(2A)-type receptors, occupation of A(1)-type receptors had to occur first. However, A(1)-receptors decreased Ca(V)2 Ca(2+)-currents, while A(2A)-type receptors enhanced current through Ca(V)1 channels. Because these channels have opposing actions on cell discharge, these differences explain in part why iSPNs may be more excitable than dSPNs. It is demonstrated that intrinsic voltage-gated currents expressed in SPNs are effectors of purinergic signaling that therefore play a role in excitability.

Kikuchi-Fujimoto disease: a case supporting a role for human herpesvirus 7 involvement in the pathogenesis.

Kikuchi's disease, also known as histiocytic necrotizing lymphadenitis, is a rare, benign, and self-limited disorder of unknown cause that is usually characterized by cervical lymphadenopathy and fever. The etiology and pathogenesis remain unknown, but the clinical presentation, course, and histologic changes suggest an immune response of T cells and histiocytes to an infectious agent. Numerous inciting agents have been proposed. However, the association between human herpesvirus 7 and Kikuchi's disease has been rarely reported as a possible etiologic agent of Kikuchi's disease. We report the case of a 24-year-old Caucasian female patient with cervical lymphadenopathy and isolated pruriginous maculo-papular lesions who was diagnosed of Kikuchi's disease in whom the presence of human herpesvirus 7 DNA was documented in the affected lymph node specimen in the absent of other viruses. Therefore, a possible etiologic relation between the Kikuchi's disease of this patient and human herpesvirus 7 was established, supporting a role for human herpesvirus 7 involvement in the pathogenesis.

Sustained leukaemic phenotype after inactivation of BCR-ABLp190 in mice.

Pharmacological inactivation of cancer genes or products is being used as a strategy for therapy in oncology. To investigate the potential role of BCR-ABLp190 cessation in leukaemia development, we generated mice carrying a tetracycline-repressible BCR-ABLp190 transgene. These mice were morphologically normal at birth, and developed leukaemias. Disease was characterized by the presence of B-cell blasts co-expressing myeloid markers, reminiscent of the human counterpart. BCR-ABLp190 activation can initiate leukaemia in both young and adult mice. Transitory expression of BCR-ABLp190 is enough to develop leukaemia. Suppression of the BCR-ABLp190 transgene in leukaemic CombitTA-p190 mice did not rescue the malignant phenotype, indicating that BCR-ABLp190 is not required to maintain the disease in mice. Similar results were obtained by inactivation of BCR-ABLp190 with STI571 (Gleevec; Novartis, East Hanover, NJ, USA) in leukaemic CombitTA-p190 mice. However, gradual suppression of BCR-ABLp190 in leukaemic CombitTA-p190 mice identified a minimum level of BCR-ABLp190 expression necessary to revert the specific block in B-cell differentiation in the leukaemic cells. Overall, the findings indicate that BCR-ABLp190 appears to cause epigenetic and/or genetic changes in tumour-maintaining cells that render them insensitive to BCR-ABLp190 inactivation.

Feedback inhibition by calcium limits the release of calcium by inositol trisphosphate in Limulus ventral photoreceptors.

Injection of inositol 1,4,5 trisphosphate (InsP3) into Limulus ventral photoreceptors elevates the concentration of intracellular calcium ions and as a consequence depolarizes the photoreceptor. This InsP3-induced elevation can be inhibited by a prior injection of calcium or InsP3 delivered 1 s earlier. Recovery from this inhibition has a half-time of between 1.5 and 5 s at 20 degrees C. Calcium released by InsP3 therefore inhibits further release of calcium from InsP3-sensitive calcium stores. This feedback inhibition may protect the calcium stores from depletion during prolonged bright illumination. Feedback inhibition, rather than periodic depletion of calcium stores, may also underlie the oscillatory bursts of InsP3-induced calcium release that have been observed in many cell types.

Recurring structural motifs in proteins with different functions.

BACKGROUND: Structures that have diverged from a common ancestor often retain functional and sequence similarity, although the latter may be very reduced. Even so, the overall fold of the structure is generally highly conserved. Now however, several have been identified of proteins that have been identified that have different functions but which have converged to a similar fold. These proteins will also have low sequence identities. RESULTS: By comparing the complete structure databank against itself, using sequence and structure alignment techniques, we have been able to identify six new examples of structurally related folds that have no apparent sequence or functional similarity. These related proteins include a family of crambin-like folds and a family of ferredoxin II folds. We found that all the similarities between structures are present in small proteins and occur as motifs within the core of a larger protein. CONCLUSION: The low sequence similarity and the lack of any obvious functional relationship between proteins with similar structures suggest that the proteins have diverged from independent ancestors. The similarities may therefore be of interest for understanding the various stereochemical and physical criteria that operate to generate a favourable fold.

SLUG (SNAI2) overexpression in embryonic development.

The Snail-related zinc-finger transcription factor, SLUG (SNAI2), is critical for the normal development of neural crest-derived cells and loss-of-function SLUG mutations have been proven to cause piebaldism and Waardenburg syndrome type 2 in a dose-dependent fashion. However, little is known about the consequences of SLUG overexpression in embryonic development. We report SLUG duplication in a child with a unique de novo 8q11.2-->q13.3 duplication associated with tetralogy of Fallot, submucous cleft palate, renal anomalies, hypotonia and developmental delay. To investigate the effects of Slug overexpression on development, we analyzed mice carrying a Slug transgene. These mice were morphologically normal at birth, inferring that Slug overexpression is not sufficient to cause overt morphogenetic defects. In the adult mice, there was a 20% incidence of sudden death, cardiomegaly and cardiac failure associated with incipient mesenchymal tumorigenesis. These findings, while not directly implicating Slug in congenital and acquired heart disease, raise the possibility that Slug overexpression may contribute to specific cardiac phenotypes and cancer development.

[Rapid recurrence of ANCA-MPO positive vasculitis after non-heart beating donor renal transplantation]. / Recurrencia rápida de una vasculitis ANCA-MPO positivo tras trasplante renal de donante en asistolia.

We report a patient with end stage renal disease with lesions compatibles with renal vasculitis antineutrophil cytoplasmic autoantibody (ANCA)-associated in phase of sclerosis that underwent renal transplantation from a non-heart beating donor after one year of haemodialysis treatment, without evidence of active vasculitis. Post-transplantation management was performed according to our protocol in this kind of donors with immunosuppressive treatment based on daclizumab, half-doses of tacrolimus, mycophenolate mofetil and steroids. In the third week the renal biopsy showed an acute necrotizing vasculitis associated with crescent glomerulonephritis. The patient was initially diagnosed of acute vascular rejection and initiated treatment with 6-metilprednisolone and anti-CD3 monoclonal anti-bodies. Two days later he developed a cutaneous purpura and the skin biopsy showed an acute necrotizing vasculitis. The determination of circulating ANCA-anti-myeloperoxidase (MPO) was positive. We initiated treatment with oral cyclophosphamide plus mycophenolate mofetil discontinuation with rapid improvement of cutaneous lesions and initiation of renal function recovery.

Liposarcoma initiated by FUS/TLS-CHOP: the FUS/TLS domain plays a critical role in the pathogenesis of liposarcoma.

The most common chromosomal translocation in liposarcomas, t(12;16)(q13;p11), creates the FUS/TLS-CHOP fusion gene. We previously developed a mouse model of liposarcoma by expressing FUS-CHOP in murine mesenchymal stem cells. In order to understand how FUS-CHOP can initiate liposarcoma, we have now generated transgenic mice expressing altered forms of the FUS-CHOP protein. Transgenic mice expressing high levels of CHOP, which lacks the FUS domain, do not develop any tumor despite its tumorigenicity in vitro and widespread activity of the EF1alpha promoter. These animals consistently show the accumulation of a glycoprotein material within the terminally differentiated adipocytes, a characteristic figure of liposarcomas associated with FUS-CHOP. On the contrary, transgenic mice expressing the altered form of FUS-CHOP created by the in frame fusion of the FUS domain to the carboxy end of CHOP (CHOP-FUS) developed liposarcomas. No tumors of other tissues were found in these transgenic mice despite widespread activity of the EF1alpha promoter. The characteristics of the liposarcomas arising in the CHOP-FUS mice were very similar to those previously observed in our FUS-CHOP transgenic mice indicating that the FUS domain is required not only for transformation but also influences the phenotype of the tumor cells. These results provide evidence that the FUS domain of FUS-CHOP plays a specific and critical role in the pathogenesis of liposarcoma.

The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice.

The characteristic t(12;16)(q13;p11) chromosomal translocation, which leads to gene fusion that encodes the FUS-CHOP chimeric protein, is associated with human liposarcomas. The altered expression of FUS-CHOP has been implicated in a characteristic subgroup of human liposarcomas. We have introduced the FUS-CHOP transgene into the mouse genome in which the expression of the transgene is successfully driven by the elongation factor 1alpha (EF1alpha) promoter to all tissues. The consequent overexpression of FUS-CHOP results in most of the symptoms of human liposarcomas, including the presence of lipoblasts with round nuclei, accumulation of intracellular lipid, induction of adipocyte-specific genes and a concordant block in the differentiation program. We have demonstrated that liposarcomas in the FUS-CHOP transgenic mice express high levels of the adipocyte regulatory protein PPARgamma, whereas it is not expressed in embryonic fibroblasts from these animals following induction to differentiation toward the adipocyte lineage, indicating that the in vitro system does not really reflect the in vivo situation and the developmental defect is downstream of PPARgamma expression. No tumors of other tissues were found in these transgenic mice despite widespread activity of the EF1alpha promoter. This establishes FUS-CHOP overexpression as a key determinant of human liposarcomas and provide the first in vivo evidence for a link between a fusion gene created by a chromosomal translocation and a solid tumor.

Measurement of cytosolic Ca2+ concentration in Limulus ventral photoreceptors using fluorescent dyes.

Several Ca-sensitive fluorescent dyes (fura-2, mag-fura-2 and Calcium Green-5N) were used to measure intracellular calcium ion concentration, Cai, accompanying light-induced excitation of Limulus ventral nerve photoreceptors. A ratiometric procedure was developed for quantification of Calcium Green-5N fluorescence. A mixture of Calcium Green-5N and a Ca-insensitive dye, ANTS, was injected in the cell and the fluorescence intensities of both dyes were used to calculate the spatial average of Cai within the light-sensitive R lobe of the photoreceptor. In dark-adapted photoreceptors, the initial Cai was 0.40 +/- 0.22 microM (SD, n = 7) as measured with fura-2. Cai peaked in the light-sensitive R lobe at 700-900 ms after the onset of an intense measuring light step, when the spatial average of Cai within the R lobe reached 68 +/- 14 and 62 +/- 37 microM (SD, n = 5) as measured with mag-fura-2 and Calcium Green-5N, respectively. The rate of Cai rise was calculated to be approximately 350 microM/s under the measuring conditions. The resting level of Mg2+ was estimated to be 1.9 +/- 0.9 mM, calculated from mag-fura-2 measurements. To investigate the effect of adapting light on the initial Cai level in the R lobe, a 1-min step of 420 nm background light was applied before each measurement. The first significant (P < 0.05) change in the initial level of Cai occurred even at the lowest adapting light intensity, which delivered approximately 3 x 10(3) effective photons/s. The relative sensitivity of the light-adapted photoreceptors was linearly related to the relative Cai on a double log plot with slope between -4.3 and -5.3. We were unable to detect a Cai rise preceding the light-activated receptor potential. The Cai rise, measured with Calcium Green-5N, lagged 14 +/- 5 ms (SD, n = 32) behind the onset of the receptor potential at room temperature in normal ASW. In the absence of extracellular Ca2+ and at 10 degrees C, this lag increased to 44 +/- 12 ms (SD, n = 17).

Abnormalities on 1q and 7q are associated with poor outcome in sporadic Burkitt's lymphoma. A cytogenetic and comparative genomic hybridization study.

Comparative genomic hybridization (CGH) studies have demonstrated a high incidence of chromosomal imbalances in non-Hodgkin's lymphoma. However, the information on the genomic imbalances in Burkitt's Lymphoma (BL) is scanty. Conventional cytogenetics was performed in 34 cases, and long-distance PCR for t(8;14) was performed in 18 cases. A total of 170 changes were present with a median of four changes per case (range 1-22). Gains of chromosomal material (143) were more frequent than amplifications (5) or losses (22). The most frequent aberrations were gains on chromosomes 12q (26%), Xq (22%), 22q (20%), 20q (17%) and 9q (15%). Losses predominantly involved chromosomes 13q (17%) and 4q (9%). High-level amplifications were present in the regions 1q23-31 (three cases), 6p12-p25 and 8p22-p23. Upon comparing BL vs Burkitt's cell leukemia (BCL), the latter had more changes (mean 4.3 +/- 2.2) than BL (mean 2.7 +/- 3.2). In addition, BCL cases showed more frequently gains on 8q, 9q, 14q, 20q, and 20q, 9q, 8q and 14q, as well as losses on 13q and 4q. Concerning outcome, the presence of abnormalities on 1q (ascertained either by cytogenetics or by CGH), and imbalances on 7q (P=0.01) were associated with a short survival.

Structure and environmental relationships of insectivorous bat assemblages in tropical Australian savannas.

Abstract Patterns in the composition of assemblages of microbat species sampled during the late dry season (the 'build-up') in north Australian savannas were assessed against a range of environmental factors as well as four a priori defined habitat types (riparian, escarpments, coastal and woodlands). Distinct species assemblages were most strongly associated with topographic and climatic variables. There were also limited associations with vegetation structure, fire and local roost potential but no associations with insects or water availability. Total species diversity at sample sites was associated with distance to rivers and rainfall. In general, species assemblages were not clearly defined and the number of significant environmental associations was relatively few. We compare these associations with those reported for bat assemblages elsewhere in Australia.

Multiple protein structure alignment.

A method was developed to compare protein structures and to combine them into a multiple structure consensus. Previous methods of multiple structure comparison have only concatenated pairwise alignments or produced a consensus structure by averaging coordinate sets. The current method is a fusion of the fast structure comparison program SSAP and the multiple sequence alignment program MULTAL. As in MULTAL, structures are progressively combined, producing intermediate consensus structures that are compared directly to each other and all remaining single structures. This leads to a hierarchic "condensation," continually evaluated in the light of the emerging conserved core regions. Following the SSAP approach, all interatomic vectors were retained with well-conserved regions distinguished by coherent vector bundles (the structural equivalent of a conserved sequence position). Each bundle of vectors is summarized by a resultant, whereas vector coherence is captured in an error term, which is the only distinction between conserved and variable positions. Resultant vectors are used directly in the comparison, which is weighted by their error values, giving greater importance to the matching of conserved positions. The resultant vectors and their errors can also be used directly in molecular modeling. Applications of the method were assessed by the quality of the resulting sequence alignments, phylogenetic tree construction, and databank scanning with the consensus. Visual assessment of the structural superpositions and consensus structure for various well-characterized families confirmed that the consensus had identified a reasonable core.

Comparison of conformational characteristics in structurally similar protein pairs.

Although it is known that three-dimensional structure is well conserved during the evolutionary development of proteins, there have been few studies that consider other parameters apart from divergence of the main-chain coordinates. In this study, we align the structures of 90 pairs of homologous proteins having sequence identities ranging from 5 to 100%. Their structures are compared as a function of sequence identity, including not only consideration of C alpha coordinates but also accessibility, Ooi numbers, secondary structure, and side-chain angles. We discuss how these properties change as the sequences become less similar. This will be of practical use in homology modeling, especially for modeling very distantly related or analogous proteins. We also consider how the average size and number of insertions and deletions vary as sequences diverge. This study presents further quantitative evidence that structure is remarkably well conserved in detail, as well as at the topological level, even when the sequences do not show similarity that is significant statistically.

Protein structural topology: Automated analysis and diagrammatic representation.

The topology of a protein structure is a highly simplified description of its fold including only the sequence of secondary structure elements, and their relative spatial positions and approximate orientations. This information can be embodied in a two-dimensional diagram of protein topology, called a TOPS cartoon. These cartoons are useful for the understanding of particular folds and making comparisons between folds. Here we describe a new algorithm for the production of TOPS cartoons, which is more robust than those previously available, and has a much higher success rate. This algorithm has been used to produce a database of protein topology cartoons that covers most of the data bank of known protein structures.

Significance of Q-wave regression after transmural acute myocardial infarction.

A total of 313 consecutive patients was studied to assess the prevalence and prognostic implications of Q-wave loss after transmural acute myocardial infarction. Heart catheterization, including single-plane left ventriculography and selective coronary arteriography, was performed before hospital discharge. After a mean follow-up of 65 (1 to 100) months, 34 patients (11%) lost their Q waves. The time interval from the acute event to the first electrocardiogram showing Q-wave disappearance was 14 (1 to 32) months. Peak creatine kinase value was significantly higher in patients who retained their Q waves than in those who lost them (1,121 +/- 813 vs 779 +/- 464 IU, respectively, p less than 0.05). Severity of coronary artery disease, as judged by the number of diseased arteries and the number of arteries with total or subtotal occlusion, was similar in both groups. However, patients showing Q-wave regression had lower left ventricular end-diastolic pressure, higher ejection fraction and fewer abnormally contracting segments than their counterparts (12 +/- 6 vs 15 +/- 7 mm Hg, p less than 0.05; 53 +/- 11 vs 44 +/- 14%, p less than 0.001; 1 +/- 1 vs 2 +/- 1 segments, p less than 0.001, respectively). In addition, no patient with normalized electrocardiogram presented with left ventricular aneurysm. Although differences in mortality, nonfatal reinfarction and new onset of angina between the 2 groups were not significant, congestive heart failure was prevalent among patients with permanent Q waves (23 vs 6%, p less than 0.05). Our findings suggest that Q-wave loss after AMI may be related to a smaller infarct size.

Allogeneic peripheral blood cell transplantation for hypereosinophilic syndrome with myelofibrosis.

Patients with hypereosinophilic syndrome (HES) display a very heterogeneous clinical picture ranging from asymptomatic cases to very aggressive forms. We report a 38-year-old woman with progressive HES who developed severe myelofibrosis and was treated by allogeneic stem cell transplantation, using peripheral blood (PBSCT) instead of bone marrow as the source of progenitor cells, after conditioning with cytoxan and busulphan. To the best of our knowledge, this is the first case of HES with myelofibrosis treated with PBSCT. The patient remains alive 8 months post-PBSCT, and bone marrow fibrosis has significantly decreased following transplantation. Bone Marrow Transplantation (2000) 25, 217-218.

High resolution light microscopy in renal pathology.

Seven hundred renal specimens embedded in epoxy resins and stained with polychromatic stains were compared with paraffin sections stained with Hematoxylin and Eosin (H & E), Perodic and Schiff, (PAS), silver, and trichrome stains. High resolution of light microscopy, never in wax histopathology, may be obtained by the use of plastic embedding and polychromatic stains. Cell boundaries, intracellular organelles, basement membranes, different cellular types, apposition of different substances, and other pathologic changes were readily recognized in a single P + P (Plastic section stained with Polychromatic stains) section, whereas paraffin sections usually needed special stains. The same plastic block may be used for transmission electron microscopy. Slightly elevated cost, special training of the technician and pathologist, and some few remaining technical difficulties are the disadvantages of this method. High resolution light microscopy methods are recommended for routine renal biopsies.