Miracle-dz/UniFAR-FTUs huggingface dataset:
The core promoter composition establishes a new dimension in developmental gene networks

Developmental processes are highly dependent on transcriptional regulation by RNA polymerase II, which initiates transcription at the core promoter. The dorsal-ventral gene regulatory network (GRN) includes multiple genes that are activated by different nuclear concentrations of the Dorsal transcription factor along the dorsal-ventral axis. Downstream core promoter element (DPE)-containing genes are conserved and highly prevalent among Dorsal target genes. Moreover, the DPE motif is functional in multiple Dorsal target genes, as mutation of the DPE results in the loss of transcriptional activity. Furthermore, analysis of hybrid enhancer-promoter constructs reveals that the core promoter composition plays a pivotal role in the transcriptional output. Importantly, we provide in vivo evidence that expression driven by the homeotic Antennapedia P2 promoter during Drosophila embryogenesis is dependent on the DPE. Taken together, we propose that transcriptional regulation results from the interplay between enhancers and core promoter composition, thus establishing a novel dimension in developmental GRNs.
Elevated expression of matrix metalloproteinase-9 and inflammatory cytokines in keratoconus patients is inhibited by cyclosporine A.

PURPOSE The present study was designed to understand the role of inflammatory cytokines secreted by corneal epithelial cells in keratoconus (KC) and the response to treatment with cyclosporine A (CyA). METHODS The study involved 129 Indian KC patients clinically graded according to Amsler-Krumeich classification and 20 healthy, nonectatic subjects as controls. Tear levels of matrix metalloproteinase-9 (MMP9), interleukin-6 (IL6), and tumor necrosis factor-α (TNFα) were measured using ELISA kits. Gene expression was measured by qPCR in corneal epithelial cells obtained by debridement from subjects undergoing ocular surface surgeries. In addition, epithelial cells were stimulated with TNFα and treated with CyA to study its role on MMP9 expression. Finally, 20 KC patients (27 eyes) with inflammatory symptoms were treated with topical CyA application. RESULTS We observed that MMP9, TNFα, and IL6 levels were strongly upregulated at the mRNA level in KC patient epithelia. Similarly, tears collected from KC patients exhibited high levels of MMP9 and IL6 protein. Cyclosporine A treatment significantly reduced the mRNA expression levels of IL6 and TNFα in both short- and long-term treatments; however, it reduced MMP9 levels only in long-term treatment in cultured corneal epithelial cells. Subsequent treatment of KC patients with CyA for approximately 6 months reduced tear MMP9 levels and led to local reduction in corneal curvatures as determined by corneal topography maps. CONCLUSIONS The data indicate that corneal epithelium contributes to elevated MMP9 and inflammatory cytokine expression in tears of KC patients. Cyclosporine A treatment reduced MMP9 and inflammatory cytokine levels in an in vitro inflammation model system. In KC patients, CyA treatment reduced MMP9 levels measured in tears with concomitant arrest of disease progression. Therefore, CyA might be a novel treatment strategy in KC patients but requires additional evaluation in larger cohorts. (ClinicalTrials.gov number, NCT01746823.).
Profile of eyelid malignancy in a Tertiary Health Care Center in North India

Context: The eyelids are affected by wide spectrum of benign and malignant lesions. Basal cell carcinoma (BCC) is the most common malignancy encountered while other malignant lesions such as sebaceous cell carcinoma and squamous cell carcinoma are rare. Data regarding geographical variation in trends of malignant eyelid tumors are presented in the current study. Settings and Design: Prospective, longitudinal, observational study was conducted from December 2011 to October 2013. Subjects and Methods: Patients with mass or growth involving eyelid managed by surgical intervention were selected for the study. Excised tissue masses were sent for histopathological examination. Results: Fifty-two cases of extraocular tumors were operated during the study period, out of which 25 cases (48%) were of eyelids. Sixteen cases (64%) were benign, and remaining 9 cases (36%) were malignant eyelid neoplasms. Benign lesions exhibited female preponderance with male:female ratio of 1:2.25. No significant difference was noted in cases of malignant lesions with male:female ratio of 1:1.25. Most common benign tumor observed was sebaceous cyst. Sebaceous gland carcinoma (4 cases) was the most common malignant neoplasm followed by squamous cell carcinoma (2 cases) and BCC, orbital melanoma, and adenocarcinoma (1 case each). Conclusions: Sebaceous gland carcinoma is more common in North India as compared to BCC and squamous cell carcinoma.
Vanishing of principal value integrals on surfaces

Abstract Principal value integrals are associated to multi-valued rational differential forms with normal crossings support on a non-singular algebraic variety. We prove their vanishing on rational surfaces in the context of a conjecture of Denef-Jacobs. As an application we obtain a strong vanishing result for candidate poles of p-adic and motivic Igusa zeta functions.
Knotting dynamics during DNA replication

The topology of plasmid DNA changes continuously as replication progresses. But the dynamics of the process remains to be fully understood. Knotted bubbles form when topo IV knots the daughter duplexes behind the fork in response to their degree of intertwining. Here, we show that knotted bubbles can form during unimpaired DNA replication, but they become more evident in partially replicated intermediates containing a stalled fork. To learn more about the dynamics of knot formation as replication advances, we used two‐dimensional agarose gel electrophoresis to identify knotted bubbles in partially replicated molecules in which the replication fork stalled at different stages of the process. The number and complexity of knotted bubbles rose as a function of bubble size, suggesting that knotting is affected by both precatenane density and bubble size.
Update in the epidemiology of Parkinson's disease

Purpose of reviewIn the past 18 months, several important studies on the epidemiology of Parkinson's disease have been published. In particular, large cohorts have identified sufficient incident patients with Parkinson's disease to study risk or protective factors of Parkinson's disease; one of the important recent events in the field is the publication of some of their findings. Recent findingsWe will first review findings of descriptive studies on the frequency of the disease and its geographic or temporal distribution. We will then summarize the findings of analytical studies dealing with risk or protective factors in the fields of dietary and lifestyle factors (cigarette smoking, coffee and tea drinking, uric acid, dairy products), environmental exposures (pesticides, lead, manganese, welding), hormonal factors (oophorectomy), vascular risk factors (diabetes, hypertension, cholesterol level), pharmacoepidemiology (NSAIDs, statins), and familial aggregation. SummaryEpidemiologic studies have consistently found that some exposures are inversely (e.g., cigarette smoking) or positively associated with Parkinson's disease (e.g., pesticides), while their findings are, at the present time, less consistent for other exposures (e.g., NSAIDs, vascular risk factors). Finally, recent studies have investigated new research fields (e.g., hormonal factors, uric acid, pharmacoepidemiology) and additional data need to be collected.
Mechanism of Stabilization of a Bacterial Collagen Triple Helix in the Absence of Hydroxyproline*

The Streptococcus pyogenes cell-surface protein Scl2 contains a globular N-terminal domain and a collagen-like domain, (Gly-Xaa-X′aa)79, which forms a triple helix with a thermal stability close to that seen for mammalian collagens. Hyp is a major contributor to triple-helix stability in animal collagens, but is not present in bacteria, which lack prolyl hydroxylase. To explore the basis of bacterial collagen triple-helix stability in the absence of Hyp, biophysical studies were carried out on recombinant Scl2 protein, the isolated collagen-like domain from Scl2, and a set of peptides modeling the Scl2 highly charged repetitive (Gly-Xaa-X′aa)n sequences. At pH 7, CD spectroscopy, dynamic light scattering, and differential scanning calorimetry of the Scl2 protein all showed a very sharp thermal transition near 36 °C, indicating a highly cooperative unfolding of both the globular and triple-helix domains. The collagen-like domain isolated by trypsin digestion showed a sharp transition at the same temperature, with an enthalpy of 12.5 kJ/mol of tripeptide. At low pH, Scl2 and its isolated collagen-like domain showed substantial destabilization from the neutral pH value, with two thermal transitions at 24 and 27 °C. A similar destabilization at low pH was seen for Scl2 charged model peptides, and the degree of destabilization was consistent with the strong pH dependence arising from the GKD tripeptide unit. The Scl2 protein contained twice as much charge as human fibril-forming collagens, and the degree of electrostatic stabilization observed for Scl2 was similar to the contribution Hyp makes to the stability of mammalian collagens. The high enthalpic contribution to the stability of the Scl2 collagenous domain supports the presence of a hydration network in the absence of Hyp.
Cell surface annexin II is a high affinity receptor for the alternatively spliced segment of tenascin-C

We have investigated the binding of soluble tenascin-C (TN-C) to several cell lines using a radioligand binding assay. Specific binding was demonstrated to U-251MG human glioma cells and to a line of bovine aortic endothelial cells, but hamster fibroblasts showed no specific binding. Recombinant proteins corresponding to specific domains of TN-C were used to map the binding site(s) in TN-C. The alternatively spliced segment (TNfnA-D) inhibited the binding of native TN-C most strongly, and itself bound to glioma and endothelial cells. Scatchard analysis of TNfnA-D binding indicated 2-5 x 10(5) binding sites per cell, with an apparent 2 nM dissociation constant. The cell surface receptor for TNfnA-D was identified as a 35-kD protein on the basis of blot binding assays and affinity chromatography of membrane extracts on native TN-C and TNfnA-D columns. Protein sequencing indicated that this 35-kD receptor was annexin II. Annexin II is well characterized as a cytoplasmic protein, so it was surprising to find it as a presumably extracellular receptor for TN-C. To confirm that it was the 35-kD receptor, we obtained purified annexin II and demonstrated its binding to TNfnA-D and TN-C at nM concentrations. Antibodies to annexin II prominently stained the external surface of live endothelial cells and blocked the binding of TNfnA-D to the cells. Thus annexin II appears to be a receptor for the alternatively spliced segment of TN-C, and may mediate cellular responses to soluble TN-C in the extracellular matrix.
Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice

Expressed in liver, aquaglyceroporin-9 (AQP9) is permeated by glycerol, arsenite, and other small, neutral solutes. To evaluate a possible protective role, AQP9-null mice were evaluated for in vivo arsenic toxicity. After injection with NaAsO2, AQP9-null mice suffer reduced survival rates (LD50, 12 mg/kg) compared with WT mice (LD50, 15 mg/kg). The highest tissue level of arsenic is in heart, with AQP9-null mice accumulating 10–20 times more arsenic than WT mice. Within hours after NaAsO2 injection, AQP9-null mice sustain profound bradycardia, despite normal serum electrolytes. Increased arsenic levels are also present in liver, lung, spleen, and testis of AQP9-null mice. Arsenic levels in the feces and urine of AQP9-null mice are only ≈10% of the WT levels, and reduced clearance of multiple arsenic species by the AQP9-null mice suggests that AQP9 is involved in the export of multiple forms of arsenic. Immunohistochemical staining of liver sections revealed that AQP9 is most abundant in basolateral membrane of hepatocytes adjacent to the sinusoids. AQP9 is not detected in heart or kidney by PCR or immunohistochemistry. We propose that AQP9 provides a route for excretion of arsenic by the liver, thereby providing partial protection of the whole animal from arsenic toxicity.
Neural Ensemble Codes for Stimulus Periodicity in Auditory Cortex

We measured the responses of neurons in auditory cortex of male and female ferrets to artificial vowels of varying fundamental frequency (f0), or periodicity, and compared these with the performance of animals trained to discriminate the periodicity of these sounds. Sensitivity to f0 was found in all five auditory cortical fields examined, with most of those neurons exhibiting either low-pass or high-pass response functions. Only rarely was the stimulus dependence of individual neuron discharges sufficient to account for the discrimination performance of the ferrets. In contrast, when analyzed with a simple classifier, responses of small ensembles, comprising 3-61 simultaneously recorded neurons, often discriminated periodicity changes as well as the animals did. We examined four potential strategies for decoding ensemble responses: spike counts, relative first-spike latencies, a binary “spike or no-spike” code, and a spike-order code. All four codes represented stimulus periodicity effectively, and, surprisingly, the spike count and relative latency codes enabled an equally rapid readout, within 75 ms of stimulus onset. Thus, relative latency codes do not necessarily facilitate faster discrimination judgments. A joint spike count plus relative latency code was more informative than either code alone, indicating that the information captured by each measure was not wholly redundant. The responses of neural ensembles, but not of single neurons, reliably encoded f0 changes even when stimulus intensity was varied randomly over a 20 dB range. Because trained animals can discriminate stimulus periodicity across different sound levels, this implies that ensemble codes are better suited to account for behavioral performance.
Evaluating monetary policy shocks in the post-1984 era

The Federal Reserve manages the short-term nominal interest rate in order to achieve its dual goals of price stability and maximum sustainable employment. This paper addresses the following question: To what extent have monetary policy shocks been helpful at stabilizing in‡ation and the unemployment gap during the post 1984 era? The paper estimates a medium-scale DSGE model with labor market frictions on post-1984 U.S. data with Bayesian techniques. I use the estimated model to back out the time series of the shocks that have hit the U.S. economy over the period 1985:Q1 - 2009:Q4 as well as the path of the unobservable potential rate of unemployment. I use the potential rate to construct a model-consistent measure of the unemployment gap. The historical decomposition of the
Suicidal Behavior and Neurological Illnesses

Objective Suicidal ideation and behavior have been associated with a variety of neurological illnesses. Studies are ongoing in combat veterans and other groups to examine possible mechanisms and pathways that account for such associations. Method This article provides a review of the literature on suicide ideation and suicidal behavior in patients with neurological illnesses including publications on veteran’s health and military medicine. Studies of suicide attempts and deaths in people with neurological illnesses are also reviewed. Results The studies summarized in this review indicate that there are important linkages between suicidal ideation and behavior and neurological conditions, including epilepsy, multiple sclerosis, and amyotrophic lateral sclerosis. Conclusion Additional studies are needed to further clarify why suicide ideation and suicidal behavior are associated with neurological diseases, in order to improve quality of life, alleviate patient distress, and prevent nonfatal and fatal suicide attempts in veteran and non-veteran populations.
Automatic Fascicle Length Estimation on Muscle Ultrasound Images With an Orientation-Sensitive Segmentation

Goal: The fascicle length obtained by ultrasound imaging is one of the crucial muscle architecture parameters for understanding the contraction mechanics and pathological conditions of muscles. However, the lack of a reliable automatic measurement method restricts the application of the fascicle length for the analysis of the muscle function, as frame-by-frame manual measurement is time-consuming. In this study, we propose an automatic measurement method to preclude the influence of nonfascicle components on the estimation of the fascicle length by using motion estimation of fascicle structures. Methods: The method starts with image segmentation using the cohesiveness of fascicle orientation as a feature, obtaining the fascicle change by tracking manually marked points on the fascicular path with the Lucas-Kanade optical flow algorithm applied on the segmented image. Results: The performance of this method was evaluated on ultrasound images of the gastrocnemius obtained from seven healthy subjects (34.4 ± 5.0 years). Waveform similarity between the manual and dynamic measurements was assessed by calculating the overall similarity with the coefficient of multiple correlations (CMC). In vivo experiments demonstrated that fascicle tracking with the orientation-sensitive segmentation (CMC = 0.97 ± 0.01) was more consistent with the manual measurements than existing automatic methods (CMC = 0.87 ± 0.10). Conclusion: Our method was robust to the interference of nonfascicle components, resulting in a more reliable measurement of the fascicle length. Significance: The proposed method may facilitate further research and applications related to real-time architectural change of muscles.
Glass structures – learning from experts

Despite the increasing research activity on structural use of glass in the past years, there is still a lack of comprehensive design codes and standards linked to real-life applications on a structural level. However, more and more ambitious buildings and structures are built every year. Thus the knowledge is out there. The aim of the presented project is to collect data on the existing design philosophy and glass failure cases. The investigation includes a survey about how practicing structural engineers deal with different design aspects of glass with a special focus on robustness and serviceability. The current document gives a brief overview about the findings of the interviews
Eocene Podocarpium (Leguminosae) from South China and its biogeographic implications

Podocarpium A. Braun ex Stizenberger is one of the most common legumes in the Neogene of Eurasia, including fossil fruits, seeds, leaves, and possible flower and pollen grains. This genus is not completely consistent with any extant genera according to gross morphological characters and poorly preserved cuticular structures reported in previous studies. The fossil pods collected from the coal-bearing series of the Changchang Basin of Hainan Island and Maoming Basin of Guangdong, South China, are examined by morphologically comparative work, with special reference to venation patterns and placental position. These distinctive features, as well as the ovule development of pods from different developmental stages and the epidermal structure of the pods, as distinguished from previous records lead to the conclusion that these fossils can be recognized as a new species of Podocarpium, P. eocenicum sp. nov. This new discovery indicates that Podocarpium had arrived in South China by the Eocene. Investigation on the fossil records of this extinct genus shows that P. eocenicum is the earliest and lowest latitude fossil data. The possible occurrence pattern of this genus is revealed as follows: Podocarpium had distributed in the South China at least in the middle Eocene, and then migrated to Europe during the Oligocene; in the Miocene this genus reached its peak in Eurasia, spreading extensively across subtropical areas to warm temperate areas; finally, Podocarpium shrank rapidly and became extinct in Eurasia during the Pliocene.
Cellular localization of thrombin receptor mRNA in rat brain: expression by mesencephalic dopaminergic neurons and codistribution with prothrombin mRNA

Cell culture studies demonstrating that the serine protease thrombin can induce neuronal and glial process retraction, glial proliferation, and changes in gene expression suggest a role for thrombin in CNS development, plasticity, and response to injury. Most cellular responses to thrombin are mediated by proteolytic activation of the cloned thrombin receptor (TR), a member of the seven transmembrane domain, G-protein-coupled receptor superfamily. As a step toward understanding the role of thrombin and its receptor in the CNS, Northern blot, in situ hybridization, and immunohistochemical techniques were used to analyze the cellular localization of TR mRNA in weanling-age rat brain. TR mRNA was broadly distributed across the neuraxis, although expression was very focal and often anatomically limited within specific neural structures. The greatest hybridization was associated with individual neurons in neocortex, cingulate/retrosplenial cortex, and subiculum, subsets of nuclei in hypothalamus, thalamus, pretectum, and ventral mesencephalon, and discrete cell layers in the hippocampus, cerebellum, and olfactory bulb. Patterns of hybridization included neuronal, glial, and ependymal cells, although white matter was uniformly negative, as were most cerebrovascular endothelial cells. Expression of TR mRNA by astroglia and dopaminergic neurons was confirmed by colocalization with immunoreactivity for glial fibrillary acidic protein (GFAP) in hippocampus and tyrosine hydroxylase in the substantia nigra. Comparison between TR and prothrombin (thrombin's precursor) cRNA hybridization demonstrated distinct but overlapping brain distributions of these transcripts, most clearly evident in postnatally developing, laminated structures. These results suggest widespread utilization of, and multiple physiologic, and possibly pathophysiologic, functions for, the thrombin/TR cell signaling system in the CNS.
Urokinase system expression in gastric carcinoma

The prognostic relevance of urokinase‐type plasminogen activator (u‐PA), u‐PA receptor (u‐PAR), and plasminogen activator inhibitor 1 (PAI‐1) in gastric carcinoma was demonstrated in an independent patient series. To the authors' knowledge,the roles of these activators as predictors of aggressive phenotypes in preoperative biopsies, Helicobacter pylori infection, and intestinal metaplasia have to date not been investigated simultaneously in resected tumors. The objectives of the current study were 1) to demonstrate the prognostic relevance of u‐PA, u‐PAR, and PAI‐1 in an independent series; 2) to evaluate u‐PA system expression in preoperative biopsy specimens compared with resected tumors; and 3) to evaluate u‐PA system expression in intestinal metaplasias and samples with H. pylori infection.
Serologic Evidence of West Nile Virus Infection in Black Bears (Ursus americanus) from New Jersey

Serum samples obtained from 51 free-ranging black bears (Ursus americanus) in northwestern New Jersey in February and March 2002 were analyzed for neutralizing antibodies to West Nile virus (WNV) and St. Lou-is encephalitis virus. Three (6%) of the black bears tested positive for WNV-neutralizing antibodies. One additional sample was positive for flavivirus-neutralizing antibodies but could not be differentiated for a specific virus type. This is the first report of WNV infection in black bears.