Miracle-dz/UniFAR-FTUs huggingface dataset:
FM19G11 Favors Spinal Cord Injury Regeneration and Stem Cell Self‐Renewal by Mitochondrial Uncoupling and Glucose Metabolism Induction

Spinal cord injury is a major cause of paralysis with no currently effective therapies. Induction of self‐renewal and proliferation of endogenous regenerative machinery with noninvasive and nontoxic therapies could constitute a real hope and an alternative to cell transplantation for spinal cord injury patients. We previously showed that FM19G11 promotes differentiation of adult spinal cord‐derived ependymal stem cells under hypoxia. Interestingly, FM19G11 induces self‐renewal of these ependymal stem cells grown under normoxia. The analysis of the mechanism of action revealed an early increment of mitochondrial uncoupling protein 1 and 2 with an early drop of ATP, followed by a subsequent compensatory recovery with activated mitochondrial metabolism and the induction of glucose uptake by upregulation of the glucose transporter GLUT‐4. Here we show that phosphorylation of AKT and AMP‐activated kinase (AMPK) is involved in FM19G11‐dependent activation of GLUT‐4, glucose influx, and consequently in stem cell self‐renewal. Small interfering RNA of uncoupling protein 1/2, GLUT‐4 and pharmacological inhibitors of AKT, mTOR and AMPK signaling blocked the FM19G11‐dependent induction of the self‐renewal‐related markers Sox2, Oct4, and Notch1. Importantly, FM19G11‐treated animals showed accelerated locomotor recovery. In vivo intrathecal sustained administration of FM19G11 in rats after spinal cord injury showed more neurofilament TUJ1‐positive fibers crossing the injured area surrounded by an increase of neural precursor Vimentin‐positive cells. Overall, FM19G11 exerts an important influence on the self‐renewal of ependymal stem progenitor cells with a plausible neuroprotective role, providing functional benefits for spinal cord injury treatment. STEM Cells2012;30:2221–2233
Animal Versus Wind Dispersal and the Robustness of Tree Species to Deforestation

Studies suggest that populations of different species do not decline equally after habitat loss. However, empirical tests have been confined to fine spatiotemporal scales and have rarely included plants. Using data from 89,365 forest survey plots covering peninsular Spain, we explored, for each of 34 common tree species, the relationship between probability of occurrence and the local cover of remaining forest. Twenty-four species showed a significant negative response to forest loss, so that decreased forest cover had a negative effect on tree diversity, but the responses of individual species were highly variable. Animal-dispersed species were less vulnerable to forest loss, with six showing positive responses to decreased forest cover. The results imply that plant-animal interactions help prevent the collapse of forest communities that suffer habitat destruction.
Subventricular Zone‐Derived Oligodendrogenesis in Injured Neonatal White Matter in Mice Enhanced by a Nonerythropoietic Erythropoietin Derivative

Perinatal hypoxia‐ischemia (HI) frequently causes white‐matter injury, leading to severe neurological deficits and mortality, and only limited therapeutic options exist. The white matter of animal models and human patients with HI‐induced brain injury contains increased numbers of oligodendrocyte progenitor cells (OPCs). However, the origin and fates of these OPCs and their potential to repair injured white matter remain unclear. Here, using cell‐type‐ and region‐specific genetic labeling methods in a mouse HI model, we characterized the Olig2‐expressing OPCs. We found that after HI, Olig2+ cells increased in the posterior part of the subventricular zone (pSVZ) and migrated into the injured white matter. However, their oligodendrocytic differentiation efficiency was severely compromised compared with the OPCs in normal tissue, indicating the need for an intervention to promote their differentiation. Erythropoietin (EPO) treatment is a promising candidate, but it has detrimental effects that preclude its clinical use for brain injury. We found that long‐term postinjury treatment with a nonerythropoietic derivative of EPO, asialo‐erythropoietin, promoted the maturation of pSVZ‐derived OPCs and the recovery of neurological function, without affecting hematopoiesis. These results demonstrate the limitation and potential of endogenous OPCs in the pSVZ as a therapeutic target for treating neonatal white‐matter injury. STEM Cells2012;30:2234–2247
Recognizing the child in child poverty

In the past few decades, a particular need for a child-centered perspective has emerged, based on evidence that children are more susceptible to environmental and social risks, and that they have different needs than adults do. This article examines issues affecting children in existing measurements and presents conceptual considerations for future work toward defining and measuring child poverty. Current definitions and measures of poverty are generally circumscribed to levels of income, satisfaction of basic needs, and issues of basic human rights; in a few cases, some well-being measures include child health, nutrition, and education. These limitations likely impede the chances that researchers will be able to capture and understand the effects of other important aspects of this phenomenon. Measures need to address the diversity of issues and dimensions that current child developmental frameworks define as the most important. A broader approach to definition and measurement that includes these developmental issues would not only affect the way we understand poverty but also inform the design of future research, social programs, and policies.
Hoxa-10 and Cyclin D3 Overexpression in the Decidual Reaction in a Superovulation Protocol in Young Adult C57BL/6J Mice

Following the performance of a superovulation protocol, multiple nodules were observed bilaterally in the uterine horns of 31 of 276 (11.2%) C57BL/6 J female mice aged 8.5 ± 0.6 (mean and standard error of mean) weeks. These lesions prevented embryo collection, and the uterine decidual reaction was suspected. Samples of pathological uteri (n = 20) and the normal genital tracts of donors treated with a similar superovulation protocol (control group, n = 10) were collected. Immunohistochemistry was performed to evaluate pancytokeratin, desmin, vimentin, progesterone receptor (PR), estrogen receptor α (ERα), Ki-67, cyclin D3 and c-Myc expression, as well as quantitative polymerase chain reaction to assess cyclin D3, Hoxa-10 and heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA expression. The uterine decidual reaction presented a high degree of structural organization and specifically affected the antimesometrial region of the endometrium. The abnormal decidual cells were large polygonal cells that were frequently polyploid or binucleated and strongly positive for desmin. Immunohistochemistry showed higher Ki-67 proliferation index and higher expression of PR and cyclin D3 in decidual cells in the antimesometrial aspect of the endometrium, compared to nondecidualized endometrial stromal cells in the mesometrial aspect of affected uteri, and compared to endometrial stromal cells in healthy uteri. High expression of cyclin D3 and Hoxa-10 mRNA was also observed in uteri affected by the decidual reaction. These results suggest that PR overexpression in endometrial stromal cells, likely due to high progesterone levels, triggers cyclin D3 and Hoxa-10 overexpression, which may be involved in the pathological mechanisms of the mouse uterine decidual reaction.
High-Thermoelectric Performance of Nanostructured Bismuth Antimony Telluride Bulk Alloys

The dimensionless thermoelectric figure of merit (ZT) in bismuth antimony telluride (BiSbTe) bulk alloys has remained around 1 for more than 50 years. We show that a peak ZT of 1.4 at 100°C can be achieved in a p-type nanocrystalline BiSbTe bulk alloy. These nanocrystalline bulk materials were made by hot pressing nanopowders that were ball-milled from crystalline ingots under inert conditions. Electrical transport measurements, coupled with microstructure studies and modeling, show that the ZT improvement is the result of low thermal conductivity caused by the increased phonon scattering by grain boundaries and defects. More importantly, ZT is about 1.2 at room temperature and 0.8 at 250°C, which makes these materials useful for cooling and power generation. Cooling devices that use these materials have produced high-temperature differences of 86°, 106°, and 119°C with hot-side temperatures set at 50°, 100°, and 150°C, respectively. This discovery sets the stage for use of a new nanocomposite approach in developing high-performance low-cost bulk thermoelectric materials.
Investigational treatment options in microscopic colitis

Collagenous and lymphocytic colitis are the two recognized major presentations of microscopic colitis. Both diseases present with chronic watery diarrhea and a chronic inflammatory infiltrate in the colonic mucosa without specific endoscopic abnormalities, and hence diagnosis is established by histology. Recent epidemiological studies suggest that microscopic colitis may affect as many patients as Crohn's disease or ulcerative colitis. The cause of these diseases is unknown; however, several lines of evidence support the hypothesis of mucosal injury from an unknown agent in the fecal stream. Due to the lack of disease causality, therapeutic management of microscopic colitis is now directed primarily at symptoms' resolution or improvement. Based on current evidence, oral budesonide represents an effective treatment option for patients with microscopic colitis to achieve and maintain remission. Other anti-inflammatory drugs such as mesalazine or bismuth subsalicylate are now under evaluation. The optimal long-term management strategy of microscopic colitis, however, remains an unsolved issue.
Effect of Histophilus somni on Heart and Brain Microvascular Endothelial Cells

Histophilus somni is a pathogenic gram-negative bacterium responsible for pneumonia and septicemia in cattle. Sequelae include infectious thrombotic meningoencephalitis (ITME), myocarditis, arthritis, and abortion. These syndromes are associated with widespread vasculitis and thrombosis, implicating a role for endothelium in pathogenesis. Histopathologic and immunohistochemical investigation of 10 natural cases of bovine H. somni myocarditis and 1 case of ITME revealed intravascular H. somni in large biofilm-like aggregates adherent to the luminal surface of microvascular endothelium. Ultrastructurally, bacterial communities were extracellular and closely associated with degenerating or contracted endothelial cells. Histophilus somni was identified by bacterial culture and/or immunohistochemistry. Western blots of the bacterial isolates revealed that they expressed the immunodominant protective 40 kDa OMP and immunoglobulin-binding protein A (IbpA) antigens. The latter is a large surface antigen and shed fibrillar antigen with multiple domains. The cytotoxic DR2Fic domain of IbpA was conserved as demonstrated by polymerase chain reaction. Treatment of endothelial cells in vitro with IbpA in crude culture supernatants or purified recombinant GST-IbpA DR2Fic (rDR2) cytotoxin induced retraction of cultured bovine brain microvascular endothelial cells. By contrast, no retraction of bovine endothelium was induced by mutant rDR2H/A with an inactive Fic motif or by a GST control, indicating that the cytotoxic DR2Fic motif plays an important role in endothelial cell retraction in vasculitis. The formation of biofilm-like aggregates by H. somni on bovine microvascular endothelium may be fundamental to its pathogenesis in heart and brain.
The Cell and Molecular Basis of Mechanical, Cold, and Inflammatory Pain

Peripheral pain pathways are activated by a range of stimuli. We used diphtheria toxin to kill all mouse postmitotic sensory neurons expressing the sodium channel Nav1.8. Mice showed normal motor activity and low-threshold mechanical and acute noxious heat responses but did not respond to noxious mechanical pressure or cold. They also showed a loss of enhanced pain responses and spontaneous pain behavior upon treatment with inflammatory insults. In contrast, nerve injury led to heightened pain sensitivity to thermal and mechanical stimuli indistinguishable from that seen with normal littermates. Pain behavior correlates well with central input from sensory neurons measured electrophysiologically in vivo. These data demonstrate that Nav1.8-expressing neurons are essential for mechanical, cold, and inflammatory pain but not for neuropathic pain or heat sensing.
An Efficient Nonviral Method to Generate Integration‐Free Human‐Induced Pluripotent Stem Cells from Cord Blood and Peripheral Blood Cells

The generation of induced pluripotent stem cells (iPSCs) provides the opportunity to use patient‐specific somatic cells, which are a valuable source for disease modeling and drug discovery. To promote research involving these cells, it is important to make iPSCs from easily accessible and less invasive tissues, like blood. We have recently reported the efficient generation of human iPSCs from adult fibroblasts using a combination of plasmids encoding OCT3/4, SOX2, KLF4, L‐MYC, LIN28, and shRNA for TP53. We herein report a modified protocol enabling efficient iPSC induction from CD34+ cord blood cells and from peripheral blood isolated from healthy donors using these plasmid vectors. The original plasmid mixture could induce iPSCs; however, the efficiency was low. The addition of EBNA1, an essential factor for episomal amplification of the vectors, by an extra plasmid greatly increased the efficiency of iPSC induction, especially when the induction was performed from αβT cells. This improvement enabled the establishment of blood‐derived iPSCs from seven healthy donors ranging in age from their 20s to their 60s. This induction method will be useful for the derivation of patient‐specific integration‐free iPSCs and would also be applicable to the generation of clinical‐grade iPSCs in the future. STEM CELLS2013;31:458–466
NuRD Blocks Reprogramming of Mouse Somatic Cells into Pluripotent Stem Cells

Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by overexpression of a defined set of transcription factors requires epigenetic changes in pluripotency genes. Nuclear reprogramming is an inefficient process and the molecular mechanisms that reset the epigenetic state during iPSC generation are largely unknown. Here, we show that downregulation of the nucleosome remodeling and deacetylation (NuRD) complex is required for efficient reprogramming. Overexpression of Mbd3, a subunit of NuRD, inhibits induction of iPSCs by establishing heterochromatic features and silencing embryonic stem cell‐specific marker genes, including Oct4 and Nanog. Depletion of Mbd3, on the other hand, improves reprogramming efficiency and facilitates the formation of pluripotent stem cells that are capable of generating viable chimeric mice, even in the absence of c‐Myc or Sox2. The results establish Mbd3/NuRD as an important epigenetic regulator that restricts the expression of key pluripotency genes, suggesting that drug‐induced downregulation of Mbd3/NuRD may be a powerful means to improve the efficiency and fidelity of reprogramming. STEM Cells2013;31:1278–1286
High throughput screening for inhibitors of REST in neural derivatives of human embryonic stem cells reveals a chemical compound that promotes expression of neuronal genes

Decreased expression of neuronal genes such as brain‐derived neurotrophic factor (BDNF) is associated with several neurological disorders. One molecular mechanism associated with Huntington disease (HD) is a discrete increase in the nuclear activity of the transcriptional repressor REST/NRSF binding to repressor element‐1 (RE1) sequences. High‐throughput screening of a library of 6,984 compounds with luciferase‐assay measuring REST activity in neural derivatives of human embryonic stem cells led to identify two benzoimidazole‐5‐carboxamide derivatives that inhibited REST silencing in a RE1‐dependent manner. The most potent compound, X5050, targeted REST degradation, but neither REST expression, RNA splicing nor binding to RE1 sequence. Differential transcriptomic analysis revealed the upregulation of neuronal genes targeted by REST in wild‐type neural cells treated with X5050. This activity was confirmed in neural cells produced from human induced pluripotent stem cells derived from a HD patient. Acute intraventricular delivery of X5050 increased the expressions of BDNF and several other REST‐regulated genes in the prefrontal cortex of mice with quinolinate‐induced striatal lesions. This study demonstrates that the use of pluripotent stem cell derivatives can represent a crucial step toward the identification of pharmacological compounds with therapeutic potential in neurological affections involving decreased expression of neuronal genes associated to increased REST activity, such as Huntington disease. Stem Cells 2013;31:1816‐1828
Practical Medical Microbiology

evidence showing similar craniopharyngioma and ada the jaw. I am delighted that a fifi appeared. It will remain the on the pathology of tumours system for some time yet. increased considerably in ti result it is now not so comfor and only reads with ease towards the centre of the bx truly a reference book r, "readers" book. ities between Congress held in Budapest during Lmantinoma of almost exclusively devoted to s steroid metabolism, their receptors th edition has effects on experimental mammary standard work and advanced human breast can of the nervous mention is made ofsome growth fa The book has main thrust of the book is to hickness; as a possible therapeutic implications. table to handle this reflects the intended readershil when opened As an outsider to this particuk ook. It is now breast cancer studies, I found 1 ather than a unsatisfactory. This was not becai presentations, which in themselves WR TIMPERLEY and well illustrated. The main de] overall lack of orientation and linkage. The briefdiscussion at the book helps no further. I suspect Practical Medical Microbiology. 13th ed. Ed JG Collee, JP Duguid, AG Fraser, BP Marmion (Pp 918; £29.50.) Churchill Livingstone. 1989. ISBN 0443-02323-8.
An overview of insulin pump therapy: appropriate use of an expensive resource

Abstract Insulin pump therapy is an option for intensive insulin therapy in patients with type l diabetes who meet the criteria described in this article. Pump therapy may assist in the reduction of haemoglobin A1c (HbA1c) and the frequency of severe hypoglycaemia. It can also lead to improvements in awareness of hypoglycaemia and quality of life. Careful assessment of patients is vital, as pump therapy is an expensive treatment option and can be dangerous if used incorrectly. Intensive education of patients who meet the criteria is essential. This will reduce possible risks associated with pump therapy. A team approach is needed, consisting of a minimum of a doctor and a diabetes educator who are experienced in pump therapy, as well as a registered dietitian who has expertise in carbohydrate counting. A psychologist is also a useful member of the team and can help with patient assessment and selection.
Genome-Scale Proteomics Reveals Arabidopsis thaliana Gene Models and Proteome Dynamics

We have assembled a proteome map for Arabidopsis thaliana from high-density, organ-specific proteome catalogs that we generated for different organs, developmental stages, and undifferentiated cultured cells. We matched 86,456 unique peptides to 13,029 proteins and provide expression evidence for 57 gene models that are not represented in the TAIR7 protein database. Analysis of the proteome identified organ-specific biomarkers and allowed us to compile an organ-specific set of proteotypic peptides for 4105 proteins to facilitate targeted quantitative proteomics surveys. Quantitative information for the identified proteins was used to establish correlations between transcript and protein accumulation in different plant organs. The Arabidopsis proteome map provides information about genome activity and proteome assembly and is available as a resource for plant systems biology.
Measurement of the Elastic Properties and Intrinsic Strength of Monolayer Graphene

We measured the elastic properties and intrinsic breaking strength of free-standing monolayer graphene membranes by nanoindentation in an atomic force microscope. The force-displacement behavior is interpreted within a framework of nonlinear elastic stress-strain response, and yields second- and third-order elastic stiffnesses of 340 newtons per meter (N m–1) and –690 Nm–1, respectively. The breaking strength is 42 N m–1 and represents the intrinsic strength of a defect-free sheet. These quantities correspond to a Young's modulus of E = 1.0 terapascals, third-order elastic stiffness of D = –2.0 terapascals, and intrinsic strength of σint = 130 gigapascals for bulk graphite. These experiments establish graphene as the strongest material ever measured, and show that atomically perfect nanoscale materials can be mechanically tested to deformations well beyond the linear regime.
Respiratory Sensation and Control of Breathing

The observation that non-chemically mediated respiratory load compensation is dependent on a state of wake- fulness suggested that the perception of the load or the conscious appreciation of the ventilatory consequences of the load- ing is required for respiratory motor output to increase. This led to studies of respiratory sensation using a variety of psy- chophysical approaches. These psychophysical studies revealed that respiratory-related physical changes are consciously appreciated and indicated that sensory information from the ventilatory apparatus does reach the cerebral cortex. This was further supported by physiological studies that demonstrated respiratory-related cortical-evoked potentials over somato- sensory regions of the brain. Studies utilizing chest wall vibration support an important role for chest wall muscle spindles in mediating respiratory sensation. Our studies have also shown that voluntarily reducing the level of ventilation at a con- stant level of chemical drive results in a progressive proportional increase in the intensity of the unpleasant sensation of respiratory discomfort and the increase in respiratory sensation is predominantly a function of the degree to which tidal volume is reduced suggesting that limiting chest expansion or thoracic displacement is the proximate cause of the un- pleasant sensation. Our observations that the sensation of dyspnea intensifies with increases in ventilation as well as when ventilation is reduced below the spontaneously adopted free breathing level can be simulated by mathematical models that suggest that respiratory drive integration depends not only on the direct effects of chemical and mechanical feedback but also on the perceptual consequences of these stimuli. In the course of daily living, the body is challenged to maintain homeostasis by changes in metabolic, mechanical, and environmental conditions. Challenges posed to the respi- ratory system are greatest by diseases of the ventilatory ap- paratus that affect the mechanical properties of the lung and chest wall and the mechanical advantage of the respiratory muscles. In the face of all of these perturbations, the respira- tory system manages to make appropriate adjustments so as to maintain ventilation at appropriate levels and preserve blood gas and acid-base homeostasis. The initial focus of our research was to identify the mechanisms of the respiratory adjustments to mechanical derangements and the interaction of chemical, neuromechanical, and, behavioral systems in the regulation of breathing.