Miracle-dz/UniFAR-FTUs huggingface dataset:
Somatotopy of the Supplementary Motor Area: Evidence from Correlation of the Extent of Surgical Resection with the Clinical Patterns of Deficit

OBJECTIVE This study, which aimed to confirm or invalidate the somatotopic organization of the supplementary motor area (SMA), correlates the pattern of clinical symptoms observed after SMA removal with the extent of resection. METHODS Eleven patients with medial precentral glioma underwent partial or complete tumoral resection of the SMA. Seven patients underwent preoperative functional magnetic resonance imaging that incorporated speech and motor tasks. During the operation, the primary motor and speech areas and pathways (in the dominant side) were identified by use of intraoperative direct cortical or subcortical stimulation, and these areas were respected. RESULTS SMA resection resulted in motor deficits, language deficits, or both; the deficits were always regressive, and they corresponded to the SMA syndrome. The topography and severity of these deficits were correlated to the extent of the SMA resection. The location of the deficit corresponded to SMA somatotopy: the representations of the lower limb, the upper limb, the face, and language (in the left-dominant SMA) were located from posterior to anterior. This somatotopy was also observed with functional magnetic resonance imaging. CONCLUSION Correlation between clinical patterns of deficit and the extent of SMA resection, guided by means of pre- and intraoperative functional methods, provides strong arguments in favor of somatotopy in this area. This knowledge should allow clinicians to base preoperative predictions of the pattern of postsurgical deficit and recovery on the planned resection, thus allowing them to inform patients accurately before the procedure.
The HML mating-type cassette of Saccharomyces cerevisiae is regulated by two separate but functionally equivalent silencers

Mating-type genes resident in the silent cassette HML at the left arm of chromosome III are repressed by the action of four SIR gene products, most likely mediated through two cis-acting sites located on opposite sides of the locus. We showed that deletion of either of these two cis-acting sites from the chromosome did not yield any detectable derepression of HML, while deletion of both sites yielded full expression of the locus. In addition, each of these sites was capable of exerting repression of heterologous genes inserted in their vicinity. Thus, HML expression is regulated by two independent silencers, each fully competent for maintaining repression. This situation was distinct from the organization of the other silent locus, HMR, at which a single silencer served as the predominant repressor of expression. Examination of identifiable domains and binding sites within the HML silencers suggested that silencing activity can be achieved by a variety of combinations of various functional domains.
In Situ Patrolling of Regulatory T Cells Is Essential for Protecting Autoimmune Exocrinopathy

Background Migration of T cells, including regulatory T (Treg) cells, into the secondary lymph organs is critically controlled by chemokines and adhesion molecules. However, the mechanisms by which Treg cells regulate organ-specific autoimmunity via these molecules remain unclear. Although we previously reported autoimmune exocrinopathy resembling Sjögren's syndrome (SS) in the lacrimal and salivary glands from C-C chemokine receptor 7 (CCR7)-deficient mice, it is still unclear whether CCR7 signaling might specifically affect the dynamics and functions of Treg cells in vivo. We therefore investigated the cellular mechanism for suppressive function of Treg cells via CCR7 in autoimmunity using mouse models and human samples. Methods and Findings Patrolling Treg cells were detected in the exocrine organs such as lacrimal and salivary glands from normal mice that tend to be targets for autoimmunity while the Treg cells were almost undetectable in the exocrine glands of CCR7 −/− mice. In addition, we found the significantly increased retention of CD4+CD25+Foxp3+ Treg cells in the lymph nodes of CCR7 −/− mice with aging. Although Treg cell egress requires sphingosine 1-phosphate (S1P), chemotactic function to S1P of CCR7−/− Treg cells was impaired compared with that of WT Treg cells. Moreover, the in vivo suppression activity was remarkably diminished in CCR7 −/− Treg cells in the model where Treg cells were co-transferred with CCR7 −/− CD25-CD4+ T cells into Rag2 −/− mice. Finally, confocal analysis showed that CCR7+Treg cells were detectable in normal salivary glands while the number of CCR7+Treg cells was extremely decreased in the tissues from patients with Sjögren's syndrome. Conclusions These results indicate that CCR7 essentially governs the patrolling functions of Treg cells by controlling the traffic to the exocrine organs for protecting autoimmunity. Characterization of this cellular mechanism could have clinical implications by supporting development of new diagnosis or treatments for the organ-specific autoimmune diseases such as Sjögren's syndrome and clarifying how the local immune system regulates autoimmunity.
Boolean constrained encoding: a new formulation and a case study

This paper provides a new, generalized approach to the problem of encoding information as vectors of binary digits. We furnish a formal definition for the Boolean constrained encoding problem, and show that this definition encompasses many particular encoding problems found in VLSI design, at various description abstraction levels. Our approach can capture equivalence and/or compatibility classes in the original symbol set to encode, by allowing symbols codes to be cubes of a Boolean space, instead of the usual minterms. Besides, we introduce a unified framework to represent encoding constraints which is more general than previous efforts. The framework is based upon a new definition of the pseudo-dichotomy concept, and is adequate to guide the solution of encoding problems through the satisfaction of constraints extracted from the original problem statement. An encoding problem case study is presented, the state assignment of synchronous finite state machines with the simultaneous consideration of state minimization. The practical comparison with well-established approaches to solve this problem in two separate steps, shows that our solution is competitive with other published results. However, the case study is primarily intended to show the feasibility of the Boolean constrained encoding problem formulation.
Paternal Occupational Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Birth Outcomes of Offspring: Birth Weight, Preterm Delivery, and Birth Defects

Agent Orange is a phenoxy herbicide that was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We studied pregnancy outcomes among wives of male chemical workers who were highly exposed to chemicals contaminated with TCDD and among wives of nonexposed neighborhood referents. For exposed pregnancies, we estimated serum TCDD concentration at the time of conception using a pharmacokinetic model. The mean TCDD concentration for workers’ births was 254 pg/g lipid (range, 3–16,340 pg/g). The mean referent concentration of 6 pg/g was assigned to pregnancies fathered by workers before exposure. A total of 1,117 live singleton births of 217 referent wives and 176 worker wives were included. Only full-term births were included in the birth weight analysis (≥37 weeks of gestation). Mean birth weight among full-term babies was similar among referents’ babies (n = 604), preexposure workers’ babies (n = 221), and exposed workers’ babies (n = 292) (3,420, 3,347, and 3,442 g, respectively). Neither continuous nor categorical TCDD concentration had an effect on birth weight for term infants after adjustment for infant sex, mother’s education, parity, prenatal cigarette smoking, and gestation length. An analysis to estimate potential direct exposure of the wives during periods of workers’ exposure yielded a nonstatistically significant increase in infant birth weight of 130 g in the highest exposure group (TCDD concentration > 254 pg/g) compared with referents (p = 0.09). Mothers’ reports of preterm delivery showed a somewhat protective association with paternal TCDD (log) concentration (odds ratio = 0.8; 95% confidence interval, 0.6–1.1). We also include descriptive information on reported birth defects. Because the estimated TCDD concentrations in this population were much higher than in other studies, the results indicate that TCDD is unlikely to increase the risk of low birth weight or preterm delivery through a paternal mechanism.
Glucose Induces Pancreatic Islet Cell Apoptosis That Requires the BH3-Only Proteins Bim and Puma and Multi-BH Domain Protein Bax

OBJECTIVE High concentrations of circulating glucose are believed to contribute to defective insulin secretion and β-cell function in diabetes and at least some of this effect appears to be caused by glucose-induced β-cell apoptosis. In mammalian cells, apoptotic cell death is controlled by the interplay of proapoptotic and antiapoptotic members of the Bcl-2 family. We investigated the apoptotic pathway induced in mouse pancreatic islet cells after exposure to high concentrations of the reducing sugars ribose and glucose as a model of β-cell death due to long-term metabolic stress. RESEARCH DESIGN AND METHODS Islets isolated from mice lacking molecules implicated in cell death pathways were exposed to high concentrations of glucose or ribose. Apoptosis was measured by analysis of DNA fragmentation and release of mitochondrial cytochrome c. RESULTS Deficiency of interleukin-1 receptors or Fas did not diminish apoptosis, making involvement of inflammatory cytokine receptor or death receptor signaling in glucose-induced apoptosis unlikely. In contrast, overexpression of the prosurvival protein Bcl-2 or deficiency of the apoptosis initiating BH3-only proteins Bim or Puma, or the downstream apoptosis effector Bax, markedly reduced glucose- or ribose-induced killing of islets. Loss of other BH3-only proteins Bid or Noxa, or the Bax-related effector Bak, had no impact on glucose-induced apoptosis. CONCLUSIONS These results implicate the Bcl-2 regulated apoptotic pathway in glucose-induced islet cell killing and indicate points in the pathway at which interventional strategies can be designed.
An intelligent system integrated with fuzzy ontology for product recommendation and retrieval

Systems that are integrated with recommendation features to support decision processes can provide a more personalized and proactive retrieval experience for users to choose among retrieval alternatives and subsequent refinement of choices. Many real-world systems call for autonomous intelligent agents acting in the face of uncertain knowledge and limited computational resources. This paper explores the development of an intelligence multi-agent based system for book recommendation and retrieval. It enlists the features of our iJADE (intelligent Java Agent-based Development Environment platform) to provide convenient Java tools and libraries for the agent components. The system possesses fuzzy reasoning features suitable for comparing, evaluating and classifying the webagents behavior. The fuzzy decision-making is based on user preferences, product feature selection and system recommendation. We can make use of the platform to build a web system integrated with the mobile multi-agent system and fuzzy ontology. The use of mobile agent technology provides a specific solution for overcoming the problem of being overloaded with too much information. User can simply enter preference information through the web browser and the backend iJADE server gets the request and sends back the relevant recommendations to the client. The simulation testing shows promising results.
Evaluation of retinal blood flow before and after panretinal photocoagulation using pattern scan laser for diabetic retinopathy

ABSTRACT Purpose: Laser speckle flowgraphy (LSFG) can measure blood flow in the ocular fundus. We analyzed the relationship between retinal blood flow and panretinal photocoagulation (PRP) in diabetic retinopathy. Methods: This retrospective observational study examined the eyes of 35 patients with proliferative diabetic retinopathy (PDR) or non-PDR (NPDR). PRP was performed using a pattern scan laser. Using LSFG, blood flow was evaluated as the mean blur rate (MBR) or the relative flow volume (RFV). We also evaluated MBR in the vessels of the optic nerve head (MBR-V), RFV at the first retinal artery (RFV-A), and RFV at the first retinal vein (RFV-V) before bifurcation. Blood flows were measured prior to treatment initiation, during each PRP session, and after PRP. Results: The total number of laser spots created was 4258 ± 461. Regression of neovascular activity at 6 months after PRP occurred in 29 (82.85%) eyes. MBR-V significantly decreased to 83.9 ± 16% (p = .0039), 79.3 ± 21% (p = .0001), and 73.5 ± 26% (p = .0001) after the first, second, and third PRP treatment sessions. MBR-V was also reduced to 75.0 ± 25% (p = .0001), 75.0 ± 25% (p = .0001), and 80.3 ± 22% (p = .0001) at 1, 3, and 6 months following PRP. During and at 6 months after the PRP treatments, RFV-A and RFV-V were also significantly reduced (p< .01). Conclusions: During and after PRP treatments using pattern scan laser, retinal blood flow was reduced. Retinal blood flow may be an auxiliary measurement for effectively evaluating PRP or PDR.
Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia.

The first two steps in the mammalian lysine-degradation pathway are catalyzed by lysine-ketoglutarate reductase and saccharopine dehydrogenase, respectively, resulting in the conversion of lysine to alpha-aminoadipic semialdehyde. Defects in one or both of these activities result in familial hyperlysinemia, an autosomal recessive condition characterized by hyperlysinemia, lysinuria, and variable saccharopinuria. In yeast, lysine-ketoglutarate reductase and saccharopine dehydrogenase are encoded by the LYS1 and LYS9 genes, respectively, and we searched the available sequence databases for their human homologues. We identified a single cDNA that encoded an apparently bifunctional protein, with the N-terminal half similar to that of yeast LYS1 and with the C-terminal half similar to that of yeast LYS9. This bifunctional protein has previously been referred to as "alpha-aminoadipic semialdehyde synthase," and we have tentatively designated this gene "AASS. " The AASS cDNA contains an open reading frame of 2,781 bp predicted to encode a 927-amino-acid-long protein. The gene has been sequenced and contains 24 exons scattered over 68 kb and maps to chromosome 7q31.3. Northern blot analysis revealed the presence of several transcripts in all tissues examined, with the highest expression occurring in the liver. We sequenced the genomic DNA from a single patient with hyperlysinemia (JJa). The patient is the product of a consanguineous mating and is homozygous for an out-of-frame 9-bp deletion in exon 15, which results in a premature stop codon at position 534 of the protein. On the basis of these and other results, we propose that AASS catalyzes the first two steps of the major lysine-degradation pathway in human cells and that inactivating mutations in the AASS gene are a cause of hyperlysinemia.
Association with pathogenic bacteria affects life-history traits and population growth in Caenorhabditis elegans

Determining the relationship between individual life-history traits and population dynamics is an essential step to understand and predict natural selection. Model organisms that can be conveniently studied experimentally at both levels are invaluable to test the rich body of theoretical literature in this area. The nematode Caenorhabditis elegans, despite being a well-established workhorse in genetics, has only recently received attention from ecologists and evolutionary biologists, especially with respect to its association with pathogenic bacteria. In order to start filling the gap between the two areas, we conducted a series of experiments aiming at measuring life-history traits as well as population growth of C. elegans in response to three different bacterial strains: Escherichia coli OP50, Salmonella enterica Typhimurium, and Pseudomonas aeruginosa PAO1. Whereas previous studies had established that the latter two reduced the survival of nematodes feeding on them compared to E. coli OP50, we report for the first time an enhancement in reproductive success and population growth for worms feeding on S. enterica Typhimurium. Furthermore, we used an age-specific population dynamic model, parameterized using individual life-history assays, to successfully predict the growth of populations over three generations. This study paves the way for more detailed and quantitative experimental investigation of the ecology and evolution of C. elegans and the bacteria it interacts with, which could improve our understanding of the fate of opportunistic pathogens in the environment.
ALS-linked mutant superoxide dismutase 1 (SOD1) alters mitochondrial protein composition and decreases protein import

Mutations in superoxide dismutase 1 (SOD1) cause familial ALS. Mutant SOD1 preferentially associates with the cytoplasmic face of mitochondria from spinal cords of rats and mice expressing SOD1 mutations. Two-dimensional gels and multidimensional liquid chromatography, in combination with tandem mass spectrometry, revealed 33 proteins that were increased and 21 proteins that were decreased in SOD1G93A rat spinal cord mitochondria compared with SOD1WT spinal cord mitochondria. Analysis of this group of proteins revealed a higher-than-expected proportion involved in complex I and protein import pathways. Direct import assays revealed a 30% decrease in protein import only in spinal cord mitochondria, despite an increase in the mitochondrial import components TOM20, TOM22, and TOM40. Recombinant SOD1G93A or SOD1G85R, but not SOD1WT or a Parkinson's disease-causing, misfolded α-synucleinE46K mutant, decreased protein import by >50% in nontransgenic mitochondria from spinal cord, but not from liver. Thus, altered mitochondrial protein content accompanied by selective decreases in protein import into spinal cord mitochondria comprises part of the mitochondrial damage arising from mutant SOD1.
Alteration of Cytokine Production during Visceral Larva Migrans by Toxascaris leonina in Mice

To determine alteration of immune responses during visceral larva migrans (VLM) caused by Toxascaris leonina at several time points, we experimentally infected mice with embryonated eggs of T. leonina and measured T-helper (Th) cell-related serial cytokine production after infection. At day 5 post infection (PI), most larvae were detected from the lungs, spleen, intestine, and muscle. Expression of thymic stromal lymphopoietin (TSLP) and CCL11 (eotaxin) showed a significant increase in most infected organs, except the intestine. However, expression of the CXCL1 (Gro-α) gene was most highly enhanced in the intestine at day 14 PI. Th1-related cytokine secretion of splenocytes showed increases at day 28 PI, and the level showed a decrease at day 42 PI. Th2-related cytokine secretion of splenocytes also showed an increase after infection; in particular, IL-5 level showed a significant increase at day 14 PI, and the level showed a decrease at day 28 PI. However, levels of Th17-related cytokines, IL-6 and IL-17A, showed gradual increases until day 42 PI. In conclusion, Th1, Th2, and Th17-related cytokine production might be important in immune responses against T. leonina VLM in experimental mice.
Constraint and Opportunity: The Genetic Basis and Evolution of Modularity in the Cichlid Mandible

Modular variation, whereby the relative degree of connectivity varies within a system, is thought to evolve through a process of selection that favors the integration of certain traits and the decoupling of others. In this way, modularity may facilitate the pace of evolution and determine evolvability. Alternatively, conserved patterns of modularity may act to constrain the rate and direction of evolution by preventing certain functions from evolving. A comprehensive understanding of the potential interplay between these phenomena will require knowledge of the inheritance and the genetic basis of modularity. Here we explore these ideas in the cichlid mandible by investigating patterns of modularity at the clade and species levels and through the introduction of a new approach, the individual level. Specifically, we assessed patterns of covariation in Lake Malawi cichlid species that employ alternate “biting” and “suction-feeding” modes of feeding and in a hybrid cross between these two ecotypes. Across the suction-feeding clade, patterns of modularity were largely conserved and reflected a functionally based pattern. In contrast, the biting species displayed a pattern of modularity that more closely matched developmental modules. The pattern of modularity present in our F2 population was very similar to the pattern exhibited by the biter, suggesting a role for dominant inheritance. We demonstrate that our individual-level metric of modularity (IMM) is a valid quantitative trait that has a nonlinear relationship with shape. IMMs for each model were used as quantitative characters to map quantitative trait loci (QTL) that underlie modularity. Our QTL analysis offers new insights into the genetic basis of modularity in these fishes that may eventually lead to the discovery of the genetic processes that delineate particular modules. In all, our findings suggest that modularity is both a constraining and an evolvable force in cichlid evolution, as distinct patterns occur between species and variation exists among individuals.
Bayesian reconstruction and use of anatomical a priori information for emission tomography

A Bayesian method is presented for simultaneously segmenting and reconstructing emission computed tomography (ECT) images and for incorporating high-resolution, anatomical information into those reconstructions. The anatomical information is often available from other imaging modalities such as computed tomography (CT) or magnetic resonance imaging (MRI). The Bayesian procedure models the ECT radiopharmaceutical distribution as consisting of regions, such that radiopharmaceutical activity is similar throughout each region. It estimates the number of regions, the mean activity of each region, and the region classification and mean activity of each voxel. Anatomical information is incorporated by assigning higher prior probabilities to ECT segmentations in which each ECT region stays within a single anatomical region. This approach is effective because anatomical tissue type often strongly influences radiopharmaceutical uptake. The Bayesian procedure is evaluated using physically acquired single-photon emission computed tomography (SPECT) projection data and MRI for the three-dimensional (3-D) Hoffman brain phantom. A clinically realistic count level is used. A cold lesion within the brain phantom is created during the SPECT scan but not during the MRI to demonstrate that the estimation procedure can detect ECT structure that is not present anatomically.