Miracle-dz/UniFAR-FTUs huggingface dataset:
Binding of major histocompatibility complex class II to the invariant chain-derived peptide, CLIP, is regulated by allelic polymorphism in class II

Major histocompatibility complex class II-associated invariant chain (Ii) provides several important functions that regulate class II expression and function. One of these is the ability to inhibit class II peptide loading early in biosynthesis. This allows for efficient class II folding and egress from the endoplasmic reticulum, and protects the class II peptide binding site from loading with peptides before entry into endosomal compartments. The ability of Ii to interact with class II and interfere with peptide loading has been mapped to Ii exon 3, which encodes amino acids 82-107. This same region of Ii has been described as a nested set of class II-associated Ii peptides (CLIPs) that are transiently associated with class II in normal cells and accumulate in human histocompatibility leukocyte antigen-DM- negative cell lines. Currently it is not clear how CLIP and the CLIP region of Ii blocks peptide binding. CLIP may bind directly to the class II peptide binding site, or may bind elsewhere on class II and modulate class II peptide binding allosterically. In this report, we show that CLIP can interact with many different murine and human class II molecules, but that the affinity of this interaction is controlled by polymorphic residues in the class II chains. Likewise, structural changes in CLIP also modulate class II binding in an allele-dependent manner. Finally, the specificity and kinetics of CLIP binding to class II molecule is similar to antigenic peptide binding to class II. These data indicate that CLIP binds to class II in an analogous fashion as conventional antigenic peptides, suggesting that the CLIP segment of Ii may actually occupy the class II peptide binding site.
A Class of F-Doubly Stochastic Markov Chains

We define a new class of processes, very useful in applications, $\mathbf{F}$-doubly stochastic Markov chains which contains among others Markov chains. This class is fully characterized by some martingale properties, and one of them is new even in the case of Markov chains. Moreover a predictable representation theorem holds and doubly stochastic property is preserved under natural change of measure.
Sertoli cell nodules in the undescended testis: a histochemical, immunohistochemical, and ultrastructural study of hyaline deposits

Aims: To document the morphology, immunohistochemical staining properties, and ultrastructural features of hyaline material in Sertoli cell nodules of undescended testis and contrast them with those of sex cord tumour with annular tubules (SCTAT), which is histologically similar. To highlight the need to distinguish these nodules from other Sertoli cell hyperplasias, such as intratubular Sertoli cell proliferations, which occur in specific clinical contexts. Materials/methods: A retrospective study of 46 orchidectomy specimens from cryptorchid testes, 27 of which contained Sertoli cell nodules. Special histochemical stains, immunohistochemical stains for type IV collagen and fibronectin, and ultrastructural examination of the hyaline material were performed using tissue from paraffin wax embedded tissue blocks. Results: The hyaline deposits in SCTAT and Sertoli cell nodules had similar staining patterns—periodic acid Schiff (PAS) and PAS-diastase positivity with variable staining of Martius scarlet blue and Masson trichrome. Type IV collagen immunoreactivity was seen in hyaline areas, although fibronectin was negative. Electron microscopy of hyaline areas confirmed a compact matrix identical to components of the basement membrane in the adjacent seminiferous tubules. Conclusion: This study describes an unusual form of Sertoli cell proliferation in undescended testes, which must be distinguished from Sertoli cell tumours and other forms of proliferation. In addition, the hyaline material within Sertoli cell nodules in the cryptorchid testis is histochemically, immunohistochemically, and ultrastructurally consistent with both matrix and fibrous components of seminiferous tubule basement membranes. Increased production of basement membrane material, with subsequent invagination into tubules, is the most likely origin of this material.
The Nitrogen Availability Interferes with Mycorrhiza-Induced Resistance against Botrytis cinerea in Tomato

Mycorrhizal plants are generally quite efficient in coping with environmental challenges. It has been shown that the symbiosis with arbuscular mycorrhizal fungi (AMF) can confer resistance against root and foliar pathogens, although the molecular mechanisms underlying such mycorrhiza-induced resistance (MIR) are poorly understood. Tomato plants colonized with the AMF Rhizophagus irregularis display enhanced resistance against the necrotrophic foliar pathogen Botrytis cinerea. Leaves from arbuscular mycorrhizal (AM) plants develop smaller necrotic lesions, mirrored also by a reduced levels of fungal biomass. A plethora of metabolic changes takes place in AMF colonized plants upon infection. Certain changes located in the oxylipin pathway indicate that several intermediaries are over-accumulated in the AM upon infection. AM plants react by accumulating higher levels of the vitamins folic acid and riboflavin, indolic derivatives and phenolic compounds such as ferulic acid and chlorogenic acid. Transcriptional analysis support the key role played by the LOX pathway in the shoots associated with MIR against B. cinerea. Interestingly, plants that have suffered a short period of nitrogen starvation appear to react by reprogramming their metabolic and genetic responses by prioritizing abiotic stress tolerance. Consequently, plants subjected to a transient nitrogen depletion become more susceptible to B. cinerea. Under these experimental conditions, MIR is severely affected although still functional. Many metabolic and transcriptional responses which are accumulated or activated by MIR such NRT2 transcript induction and OPDA and most Trp and indolic derivatives accumulation during MIR were repressed or reduced when tomato plants were depleted of N for 48 h prior infection. These results highlight the beneficial roles of AMF in crop protection by promoting induced resistance not only under optimal nutritional conditions but also buffering the susceptibility triggered by transient N depletion.
Comparing the Quality of Death for Hospice and Non-Hospice Cancer Patients

In this secondary analysis of data from the National Hospice Study (NHS), a new measure, quality of death (QOD), was developed by weighting reports of cancer patients' last 3 days of life by what patients wanted their last 3 days to be like. Using analysis of covariance, the QOD scores were higher for terminally ill patients in hospices (either home-care [HC] or hospital-based [HB]) than similar patients who received conventional care (CC). The results are discussed in terms of verification of the hospice philosophy and other uses for a quality of death measure.
Endostatin has novel ATPase activity, which its anti-angiogenic and anti-tumor activities

Endostatin is an endogenous angiogenesis inhibitor with broad-spectrum anti-tumor activities. Although the molecular mechanisms of endostatin have been extensively explored, the intrinsic biochemical characteristics of endostatin are not completely understood. Here we revealed for the first time that endostatin embedded novel ATPase activity. Moreover, mutagenesis study showed that the ATPase activity of endostatin mutants positively correlated with effects on endothelial cell activities and tumor growth. E-M, an endostatin mutant with higher ATPase activity than that of wild type endostatin, significantly increased endostatin-mediated inhibitory effects on endothelial cell proliferation, migration, tube formation and adhesion. In vivo study showed that E-M displayed enhanced anti-tumor effects compared with wild type. On the other hand, K96A, K96R and E176A, endostatin mutants with lower ATPase activities than that of wild type, showed reduced or comparable effects on targeting both in vitro endothelial cell activities and in vivo tumor angiogenesis and tumor growth. Furthermore, endostatin and its mutants exhibited distinct abilities in regulations of gene expression (Id1, Id3), cell signaling (Erk, p38 and Src phosphorylation), and intracellular ATP levels. Collectively, our study demonstrates that endostatin has novel ATPase activity, which mediates its anti-angiogenic and anti-tumor activities, suggesting that construction of endostatin analogues with high ATPase activity may provide a new direction for the development of more potent anti-angiogenic drugs. 5 mutant with higher ATPase activity, showed the more potent anti-tumor and anti-angiogenic effects. Collectively, our study demonstrates that endostatin has novel ATPase activity, which mediates the anti-angiogenic and anti-tumor effects of endostatin. indicated proteins for 1 hour, and stimulated with VEGF 165 for 10 min. The overall and phosphorylation levels of Erk, p38, and Src were examined by Western blot. D, were treated
A restricted population of CB1 cannabinoid receptors with neuroprotective activity

Significance Cannabinoids and their endogenous counterparts, the so-called endocannabinoids, promote neuroprotection in laboratory animals by engaging CB1 cannabinoid receptors, one of the most abundant types of receptors in the brain. However, the assessment of the physiological relevance and therapeutic potential of the CB1 receptor in neurological diseases is hampered, at least in part, by the lack of knowledge of the neuron-population specificity of CB1 receptor action. This study shows that a unique and well-defined population of CB1 receptors, namely that located on glutamatergic terminals, plays a key neuroprotective role in the mouse brain. This finding opens a new conceptual view on how the CB1 receptor evokes neuroprotection, and provides preclinical support for improving the development of cannabinoid-based neuroprotective therapies. The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain. Of note, CB1 receptors are expressed at the synapses of two opposing (i.e., GABAergic/inhibitory and glutamatergic/excitatory) neuronal populations, so the activation of one and/or another receptor population may conceivably evoke different effects. Despite the widely reported neuroprotective activity of the CB1 receptor in animal models, the precise pathophysiological relevance of those two CB1 receptor pools in neurodegenerative processes is unknown. Here, we first induced excitotoxic damage in the mouse brain by (i) administering quinolinic acid to conditional mutant animals lacking CB1 receptors selectively in GABAergic or glutamatergic neurons, and (ii) manipulating corticostriatal glutamatergic projections remotely with a designer receptor exclusively activated by designer drug pharmacogenetic approach. We next examined the alterations that occur in the R6/2 mouse, a well-established model of Huntington disease, upon (i) fully knocking out CB1 receptors, and (ii) deleting CB1 receptors selectively in corticostriatal glutamatergic or striatal GABAergic neurons. The data unequivocally identify the restricted population of CB1 receptors located on glutamatergic terminals as an indispensable player in the neuroprotective activity of (endo)cannabinoids, therefore suggesting that this precise receptor pool constitutes a promising target for neuroprotective therapeutic strategies.
A Random Walk Down the Genomes: DNA Evolution in Valis

The authors propose a new software system that incorporates biological data and domain-specific knowledge and show how biologists can use it to model, analyze, and experiment with genomic evolutionary processes. A better understanding of biology will come through information-theoretic studies of genomes that provide insights into DNA's role in governing metabolic and regulatory pathways. Understanding the evolutionary processes that act on these "codes of life" requires the ability to analyze vast amounts of continually generated genomic data. Researchers in the emerging bioinformatics discipline require more complex mechanisms to investigate the full ensemble of available biological facts. To meet this challenge, New York University's Bioinformatics Group is creating a computational environment called Valis, the vast active living intelligent system. Valis is designed to solve the immediate genomic and proteomic problems that the biological community currently faces, while remaining flexible enough to adapt to the maturing bioinformatics field.
Gr-1 Ab Administered after Bone Marrow Transplantation plus Thymus Transplantation Suppresses Tumor Growth by Depleting Granulocytic Myeloid-Derived Suppressor Cells

It has been shown that allogeneic intra-bone marrow–bone marrow transplantation (IBM-BMT) plus thymus transplantation (TT) is effective in treating recipients with malignant tumors. Although TT increases the percentage of T cells in the early term after BMT, the myeloid-derived suppressor cells (MDSCs) are still the dominant population. We used the Gr-1 Ab to deplete the granulocytic MDSCs (G-MDSCs) in tumor-bearing mice that had received BMT+TT. Two weeks after the BMT, the mice injected with Gr-1 Ab showed smaller tumors than those in the control group. In addition, Gr-1 Ab significantly increased the percentages and numbers of CD4+ and CD8+ T cells, and decreased the percentages and numbers of MDSCs and G-MDSCs. No side effects of the Gr-1 Ab on recipient or donor thymus were observed. These findings indicate that Gr-1 Ab administered after BMT+TT may enhance the effectiveness of tumor suppression.
Influence of habitual dietary fibre intake on the responsiveness of the gut microbiota to a prebiotic: protocol for a randomised, double-blind, placebo-controlled, cross-over, single-centre study

Introduction The commensal gut microbiota have been shown to have an impact on human health as aberrant gut microbiota have been linked to disease. Dietary constituents are influential in shaping the gut microbiota. Diet-specific therapeutic strategies may therefore play a role in optimising human health via beneficial manipulation of the gut microbiota. Research has suggested that an individual's baseline gut microbiota composition may influence how the gut microbiota respond to a dietary intervention and individuals with differing habitual dietary intakes appear to have distinct baseline gut microbiota compositions. The responsiveness of the gut microbiota may therefore be influenced by habitual dietary intakes. This study aims to investigate what influence differing habitual dietary fibre intakes have on the responsiveness of the gut microbiota to a prebiotic intervention. Methods and analysis In this randomised, double-blind, placebo-controlled, cross-over, single-centre study, 20 low dietary fibre (dietary fibre intake <18 g/day for females and <22 g/day for males) and 20 high dietary fibre (dietary fibre intake ≥25 g/day for females and ≥30 g/day for males) consumers will be recruited. Participants will be randomised to a placebo (Glucidex 29 Premium) or a prebiotic (Synergy 1) intervention for 3 weeks with a 3-week washout followed by 3 weeks of the alternative intervention. Outcome measures of gut microbiota composition (using 16S rRNA gene sequencing) and functional capacity (faecal short chain fatty acid concentrations and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt)) as well as appetite (visual analogue scale appetite questionnaire) will be assessed at the beginning and end of each intervention phase. Ethics and dissemination The Massey University Human Ethics Committee approved this study (Massey University HEC: Southern A application—15/34). Results will be disseminated through peer-review journal publications, conference presentations and a summary of findings will be distributed to participants. Trial registration number ACTRN12615000922572; Pre-results.
On linear independence for integer translates of a finite number of functions

We investigate linear independence of integer translates of a finite number of compactly supported functions in two cases. In the first case there are no restrictions on the coefficients that may occur in dependence relations. In the second case the coefficient sequences are restricted to be in some lp space (1 ≦ p ≦ ∞) and we are interested in bounding their lp-norms in terms of the Lp-norm of the linear combination of integer translates of the basis functions which uses these coefficients. In both cases we give necessary and sufficient conditions for linear independence of integer translates of the basis functions. Our characterization is based on a study of certain systems of linear partial difference and differential equations, which are of independent interest.
Intravenous dexmedetomidine prolongs bupivacaine spinal analgesia.

BACKGROUND The prolongation of spinal anesthesia by using clonidine through the oral, intravenous and spinal route has been known. The new alpha 2 agonist, dexmedetomidine has been proved to prolong the spinal anesthesia through the intrathecal route. We hypothesized that dexmedetomidine when administered intravenously following spinal block, also prolongs spinal analgesia. METHODS 48 patients were randomly allocated into two equal groups following receiving spinal isobaric bupivacaine 12.5 mg. Patients in group D received intravenously a loading dose of 1 microg/kg dexmedetomidine over 10 min and a maintenance dose of 0.5 microg/kg/hr. Patients in group C (the control group) received normal saline. The regression times to reach S1 sensory level and Bromage 0 motor scale, hemodynamic changes and the level of sedation were recorded. RESULTS The duration of sensory block was longer in intravenous dexmedetomidine group compared with control group (261.5 +/- 34.8 min versus 165.2 +/- 31.5 min, P < 0.05). The duration of motor block was longer in dexmedetomidine group than control group (199 +/- 42.8 min versus 138.4 +/- 31.3 min, P < 0.05). CONCLUSION Intravenous dexmedetomidine administration prolonged the sensory and motor blocks of bupivacaine spinal analgesia with good sedation effect and hemodynamic stability.
Up and down states

Operationally, up and down states refer to the observation that neurons have two preferred subthreshold membrane potentials, both subthreshold for action potential generation. The most common method of detecting these states is the so-called all-points histogram (Cowan and Wilson, 1994; Wilson and Kawaguchi, 1996; Pare et al., 1998). This method, borrowed from the study of single channel currents, plots the frequency of occurrence of various values of membrane potential for every point in a digitized record. Figure 1 shows a typical example for a striatal spiny neuron, and for a cortical pyramidal cell in layer V, recorded simultaneously. The histogram to the left of each one shows the amount of time the cell spends at each value of membrane potential. Both cells toggle between two preferred membrane potentials, one very hyperpolarized (Down state), and one more depolarized (Up state). In both cells, the Up state is only a few millivolts from the action potential threshold. Usually, membrane potential fluctuations around the Up state are of higher amplitude, whereas the Down state is relatively free of noise. Figure 1 Up and down states. Up and Down states have been most often studied in animals anesthetized with urethane or other anesthetics that induce slow coherent oscillations in the cortex similar to those seen during sleep or anesthesia (e.g. Steriade et al., 1993; Steriade et al., 2001; Mahon et al., 2006; Destexhe et al. 2007). Because of this, Up and Down states are sometimes used as a synonym for slow oscillations. That usage is avoided here, and, Up and Down states will refer only to the set of cellular and network properties that causes neurons to respond to synaptic input in a two-state manner. These cellular properties arise from ionic conductances that are always present in the cell, and can continue to influence cellular activity in other circumstances not associated with slow oscillations. For example, much of the work on Up and Down states has been obtained in tissue slices, which are neither anethetized nor asleep, and often not showing any slow oscillations. Neurons may exhibit two-state behavior because of their intrinsic properties, or because they are in a network that imposes it on them, or both, and may be expressed as a part of a variety of activity states.
The Role of Pre-Operative and Post-Operative Glucose Control in Surgical-Site Infections and Mortality

Background and Objective The impact of glucose control on surgical-site infection (SSI) and death remains unclear. We examined how pre- and post-operative glucose levels and their variability are associated with the risk of SSI or in-hospital death. Methods This retrospective cohort study employed data on 13,800 hospitalized patients who underwent a surgical procedure at a large referral hospital in New York between 2006 and 2008. Over 20 different sources of electronic data were used to analyze how thirty-day risk of SSI and in-hospital death varies by glucose levels and variability. Maximum pre- and post-operative glucose levels were determined for 72 hours before and after the operation and glucose variability was defined as the coefficient of variation of the glucose measurements. We employed logistic regression to model the risk of SSI or death against glucose variables and the following potential confounders: age, sex, body mass index, duration of operation, diabetes status, procedure classification, physical status, emergency status, and blood transfusion. Results While association of pre- and post-operative hyperglycemia with SSI were apparent in the crude analysis, multivariate results showed that SSI risk did not vary significantly with glucose levels. On the other hand, in-hospital deaths were associated with pre-operative hypoglycemia (OR = 5.09, 95% CI (1.80, 14.4)) and glucose variability (OR = 1.14, 95% CI (1.03, 1.27) for 10% increase in coefficient of variation). Conclusion In-hospital deaths occurred more often among those with pre-operative hypoglycemia and higher glucose variability. These findings warrant further investigation to determine whether stabilization of glucose and prevention of hypoglycemia could reduce post-operative deaths.