Miracle-dz/UniFAR-FTUs huggingface dataset:
A guide to super-resolution fluorescence microscopy

For centuries, cell biology has been based on light microscopy and at the same time been limited by its optical resolution. However, several new technologies have been developed recently that bypass this limit. These new super-resolution technologies are either based on tailored illumination, nonlinear fluorophore responses, or the precise localization of single molecules. Overall, these new approaches have created unprecedented new possibilities to investigate the structure and function of cells.
Silencing of phosphoglucose isomerase/autocrine motility factor decreases U87 human glioblastoma cell migration

Phosphoglucose isomerase/autocrine motility factor (PGI/AMF) is secreted by tumors and influences tumor growth and metastasis. In order to investigate the effects of silencing PGI/AMF on the migration and the sphere forming abilities of human glioblastoma U87 cells, as well as on the side population cells (SPCs), PGI/AMF was silenced using siRNA. Western blot analysis and RT-qPCR were used to assess the expression of PGI/AMF, Akt and SRY (sex determining region Y)-box 2 (SOX2). Wound healing, migration and tumorsphere formation assays were performed to assess invasion and metastatic potential. The proportion of SPCs was determined using Hoechst 33342 dye and flow cytometric analysis. PGI/AMF silencing inhibited the wound healing capacity and migration ability of U87 cells by 52.6 and 80.4%, respectively, compared with the scrambled siRNA (both P<0.001). Silencing of PGI/AMF decreased the proportion of SPCs in the U87 cells by 80.9% (P<0.01). The silencing of PGI/AMF decreased the number and size of tumorspheres by 53.1 and 39.9%, respectively, compared with the scrambled siRNA (both P<0.01). The silencing of PGI/AMF decreased the levels of phosphorylated Akt (−71.9%, P<0.001) compared with the scrambled siRNA, as well as the levels of the stemness marker, SOX2 (−61.7%, P<0.01). Taken together, these findings suggest that PGI/AMF silencing decreases migration, tumorsphere formation as well as the proportion of SPCs in glioblastoma U87 cells. We suggest that the Akt pathway is involved, and our results provide a potential new target for the treatment of glioblastoma.
Catalysis-dependent stabilization of Bre1 fine-tunes histone H2B ubiquitylation to regulate gene transcription

Monoubiquitylation of histone H2B on Lys123 (H2BK123ub1) plays a multifaceted role in diverse DNA-templated processes. Wozniak and Strahl show that H2BK123ub1 is regulated through the control of Bre1 protein stability. Bre1 stability is primarily controlled through its association with the PAF complex. Using a domain in Rtf1 that stabilizes Bre1, they show that inappropriate Bre1 levels lead to defects in gene regulation. These data uncover a novel quality control mechanism used by the cell to maintain proper Bre1 and H2BK123ub1 levels, thereby ensuring proper control of gene expression.
Piezoelectric Nanoparticle-Assisted Wireless Neuronal Stimulation

Tetragonal barium titanate nanoparticles (BTNPs) have been exploited as nanotransducers owing to their piezoelectric properties, in order to provide indirect electrical stimulation to SH-SY5Y neuron-like cells. Following application of ultrasounds to cells treated with BTNPs, fluorescence imaging of ion dynamics revealed that the synergic stimulation is able to elicit a significant cellular response in terms of calcium and sodium fluxes; moreover, tests with appropriate blockers demonstrated that voltage-gated membrane channels are activated. The hypothesis of piezoelectric stimulation of neuron-like cells was supported by lack of cellular response in the presence of cubic nonpiezoelectric BTNPs, and further corroborated by a simple electroelastic model of a BTNP subjected to ultrasounds, according to which the generated voltage is compatible with the values required for the activation of voltage-sensitive channels.
Airflow limitation as a risk factor for low bone mineral density and hip fracture

Aim To investigate whether airflow limitation is associated with bone mineral density (BMD) and risk of hip fractures. Methods A community sample of 5,100 subjects 47–48 and 71–73 years old and living in Bergen was invited. Participants filled in questionnaires and performed a post-bronchodilator spirometry measuring forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). All attendants were invited to have a BMD measurement of the hip. During 10 years of follow-up, information on death was collected from the Norwegian Cause of Death Registry, and incident hip fractures were registered from regional hospital records of discharge diagnoses and surgical procedure codes. Results The attendance rate was 69% (n=3,506). The prevalence of chronic obstructive pulmonary disease (COPD) (FEV1/FVC<0.7) was 9%. In multiple logistic regression, the lowest quartile of BMD versus the three upper was significantly predicted by FEV1/FVC<0.7 and FEV1% predicted (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.11 to 2.25, and OR per increase of 10%: 0.92, 95% CI: 0.86 to 0.99, respectively). Hip fracture occurred in 126 (4%) participants. In a Cox regression analysis, FEV1% predicted was associated with a lowered risk of hip fracture (hazard ratio per increase of 10%: 0.89, 95% CI: 0.79 to 0.997). Conclusion Airflow limitation is positively associated with low BMD and risk of hip fracture in middle-aged and elderly.
Mitonuclear interactions: evolutionary consequences over multiple biological scales

Fundamental biological processes hinge on coordinated interactions between genes spanning two obligate genomes—mitochondrial and nuclear. These interactions are key to complex life, and allelic variation that accumulates and persists at the loci embroiled in such intergenomic interactions should therefore be subjected to intense selection to maintain integrity of the mitochondrial electron transport system. Here, we compile evidence that suggests that mitochondrial–nuclear (mitonuclear) allelic interactions are evolutionarily significant modulators of the expression of key health-related and life-history phenotypes, across several biological scales—within species (intra- and interpopulational) and between species. We then introduce a new frontier for the study of mitonuclear interactions—those that occur within individuals, and are fuelled by the mtDNA heteroplasmy and the existence of nuclear-encoded mitochondrial gene duplicates and isoforms. Empirical evidence supports the idea of high-resolution tissue- and environment-specific modulation of intraindividual mitonuclear interactions. Predicting the penetrance, severity and expression patterns of mtDNA-induced mitochondrial diseases remains a conundrum. We contend that a deeper understanding of the dynamics and ramifications of mitonuclear interactions, across all biological levels, will provide key insights that tangibly advance our understanding, not only of core evolutionary processes, but also of the complex genetics underlying human mitochondrial disease.
Unique characteristics of histone deacetylase inhibitors in reactivation of latent HIV-1 in Bcl-2-transduced primary resting CD4+ T cells.

OBJECTIVES The latent reservoir for HIV-1 in resting memory CD4+ T cells is a major barrier to eradication. In vitro models involving transformed cell lines have been used to search for small molecules that reactivate latent HIV-1. Histone deacetylase (HDAC) inhibitors can reverse HIV-1 latent infection. Most studies on HDAC inhibitors have been performed in cell line models that differ in important aspects from the resting CD4+ T cells that harbour latent HIV-1 in vivo. Therefore, we evaluated the potency and kinetics of HDAC inhibitors in a primary cell model of HIV-1 latency that involves resting CD4+ T cells. METHODS A green fluorescent protein (GFP)-expressing reporter virus NL4-3-Δ6-drGFP was used to generate latent infection in Bcl-2-transduced primary CD4+ T cells. Seventeen HDAC inhibitors were tested in this primary cell model. The effects of these HDAC inhibitors on the reactivation of latent HIV-1 were determined and compared with anti-CD3 and anti-CD28 co-stimulation. RESULTS In Bcl-2-transduced primary CD4+ T cells, short-term treatment with HDAC inhibitors resulted in very limited reactivation of latent HIV-1, while prolonged treatment greatly enhanced drug efficacy. The effects of HDAC inhibitors in reactivating latent HIV-1 correlated with their inhibitory effects on class I HDACs. Importantly, HIV-1 reactivated by HDAC inhibitors can quickly re-establish latent infection upon drug removal. CONCLUSIONS We identified unique features of HDAC inhibitor-induced reactivation of latent HIV-1 in primary CD4+ T cells. Our findings may be useful for the design of eradication trials.
Considerations in Nerve Repair

Some nerve injuries require repair in order to regain sensory or motor function. Although this article focuses primarily on trigeminal nerve (TN) injuries and repairs, the facts presented may apply to any peripheral nerve repair. The primary indications for nerve repair or grafting are 1) an injury or continuity defect in a nerve, as a result of trauma, pathology, surgery, or disease, that cannot regain normal function without surgical intervention and 2) loss of normal neurologic function, resulting in anesthesia, paresthesia, dysesthesia, or paralysis, that cannot be corrected by nonsurgical treatment. In some nerve injuries (e.g., neurapraxia), the nerve regains sensory or motor function unless irreversible compression, neuroma (axonotmesis), or transection (neurotmesis) occurs. In more severe injuries, there may be significant loss of nerve substance (continuity defect), or a section of nerve may need to be removed to expose normal nerve tissue in preparation for nerve repair. Thus, nerve repair and nerve grafting procedures may be required to provide continuity between the proximal and distal portions of the nerve. The 3 major branches of the TN that can be involved in injuries are the inferior alveolar nerve (IAN), lingual nerve (LN), and infraorbital nerve (ION). The most common types of injury to the IAN and LN are iatrogenic, related to removal of impacted teeth (Figure ​(Figure11), orthognathic surgery (jaw repositioning), periodontics (gum surgery), endodontics (root canal procedures), dental implants, curettage of intrabony lesions, partial or total resection of the mandible or tongue in tumor removal, and other surgical procedures. Injuries to the ION are more commonly caused by trauma to the middle third of the face, partial or total maxillectomy and orbital exenteration during resection of benign or malignant tumors, or inadvertent nerve injury during maxillary and midface osteotomy procedures. Nerve injuries that are more difficult to manage include severe stretch injuries and chemical injuries such as those that occur when alcohol, steroid, or other caustic agents are injected into or around nerves. The nature and extent of the nerve pathology will influence the type and quality of repair (1). Figure 1 A large traumatic neuroma (N) is seen 1 year after removal of the third molar. Note the significant atrophy of the distal (D) portion of the nerve and the mismatch in size compared with the proximal (P) portion of the nerve.
A genome‐wide association study of 23 agronomic traits in Chinese wheat landraces

Uncovering the genetic basis of agronomic traits in wheat landraces is important for ensuring global food security via the development of improved varieties. Here, 723 wheat landraces from 10 Chinese agro-ecological zones were evaluated for 23 agronomic traits in six environments. All accessions could be clustered into five subgroups based on phenotypic data via discriminant function analysis, which was highly consistent with genotypic classification. A genome-wide association study was conducted for these traits using 52 303 DArT-seq markers to identify marker-trait associations and candidate genes. Using both the general linear model and the mixed linear model, 149 significant markers were identified for 21 agronomic traits based on best linear unbiased prediction values. Considering the linkage disequilibrium decay distance in this study, significant markers within 10 cM were combined as a quantitative trait locus (QTL), with a total of 29 QTL identified for 15 traits. Of these, five QTL for heading date, flag leaf width, peduncle length, and thousand kernel weight had been reported previously. Twenty-five candidate genes associated with significant markers were identified. These included the known vernalization genes VRN-B1 and vrn-B3 and the photoperiod response genes Ppd and PRR. Overall, this study should be helpful in elucidating the underlying genetic mechanisms of complex agronomic traits and performing marker-assisted selection in wheat.
Zero-Velocity Detection—An Algorithm Evaluation

In this paper, we investigate the problem of detecting-time epochs when zero-velocity updates can be applied in a foot-mounted inertial navigation (motion-tracking) system. We examine three commonly used detectors: the acceleration-moving variance detector, the acceleration-magnitude detector, and the angular rate energy detector. We demonstrate that all detectors can be derived within the same general likelihood ratio test (LRT) framework, given the different prior knowledge about the sensor signals. Further, by combining all prior knowledge, we derive a new LRT detector. Subsequently, we develop a methodology to evaluate the performance of the detectors. Employing the developed methodology, we evaluate the performance of the detectors using leveled ground, slow (approximately 3 km/h) and normal (approximately 5 km/h) gait data. The test results are presented in terms of detection versus false-alarm probability. Our preliminary results show that the new detector performs marginally better than the angular rate energy detector that outperforms both the acceleration-moving variance detector and the acceleration-magnitude detector.
ON MIXED PROJECTIVE CURVES

Let f(z,¯) be a mixed polar homogeneous polynomial of n variables z = (z1, . . . , zn). It defines a projective real algebraic va- riety V := {(z) 2 CP n 1 | f(z,¯) = 0} in the projective space CP n 1 . The behavior is different from that of the projective hypersurface. The topology is not uniquely determined by the degree of the variety even if V is non-singular. We study a basic property of such a variety.
Diffusion and phase relations in the systems Ti-Si-C and Ti-Si-N

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Seasonal Variation of Group a Streptococcus (GAS) - Related Necrotising Fasciitis Cases in a UK Teaching Hospital

Objectives: Necrotizing fasciitis is a diverse syndrome primarily involving the fascia but also occasionally the overlying skin and underlying muscles. Non-necrotising lower limb cellulitis has been reported to have a marked seasonal variation in our area. We are describing the seasonal variation of our necrotising fasciitis cases. Methods: The medical records of all the patients that were admitted to our institution with a diagnosis of necrotizing fas- ciitis, from January 1994 to December 2003, were retrospectively reviewed. Results: The necrotising fasciitis infections peaked every year in the spring time, as previously described for cellulitis. The increased incidence was only apparent for group A streptococcus related necrotising fasciitis cases. The diagnosis carried 21% mortality during the same admission. Overall, 39% of the patients had a bad outcome, defined as either death during the same admission, limb amputation or severe disability. 73% of patients who experienced a bad outcome were found to have Group A streptococcus compared to only 41% of the patients in the good outcome group. Conclusions: A seasonal variation was noted for Group A streptococcus associated necrotising fasciitis, that remains a le- thal condition. As patients with Group A streptococcus associated necrotising fasciitis tend to have a worse outcome in our series, increased awareness and targeted antibiotic therapy may enhance clinical outcomes. Knowledge of microbiol- ogy might also inform infection control decisions.
Anaerobic Ammonia-Oxidizing Bacteria and Related Activity in Baltimore Inner Harbor Sediment

ABSTRACT The discovery of bacteria capable of anaerobic ammonia oxidation (anammox) has generated interest in understanding the activity, diversity, and distribution of these bacteria in the environment. In this study anammox activity in sediment samples obtained from the Inner Harbor of Baltimore, Md. , was detected by 15N tracer assays. Anammox-specific oligonucleotide primer sets were used to screen a Planctomycetales-specific 16S rRNA gene library generated from sediment DNA preparations, and four new anammox bacterial sequences were identified. Three of these sequences form a cohesive new branch of the anammox group, and the fourth sequence branches separately from this group. Denaturing gradient gel electrophoresis analysis of sediment incubated with anammox-specific media confirmed the presence of the four anammox-related 16S rRNA gene sequences. Evidence for the presence of anammox bacteria in Inner Harbor sediment was also obtained by using an anammox-specific probe in fluorescence in situ hybridization studies. To our knowledge, this is the first report of anammox activity and related bacterial 16S rRNA gene sequences from the Chesapeake Bay basin area, and the results suggest that this pathway plays an important role in the nitrogen cycle of this estuarine environment. Furthermore, the presence of these bacteria and their activity in sediment strengthen the contention that anammox-related Plactomycetales are globally distributed.
Lessons from studies on focal segmental glomerulosclerosis: an important role for parietal epithelial cells?

Glomerular diseases are caused by multiple mechanisms. Progressive glomerular injury is characterized by the development of segmental or global glomerulosclerosis independent of the nature of the underlying renal disease. Most studies on glomerular disease focus on the constituents of the filtration barrier (podocytes, glomerular basement membrane (GBM), endothelial cells) or the mesangial cells. Little attention is given to the epithelial cells lining Bowman's capsule, the so called parietal epithelial cells (PECs). This ‘lack of attention’ is partly explained by the presumed ‘passive’ function of PECs, which are large, flattened cells that cover Bowman's capsule in a single cell layer and form a barrier between the ultrafiltrate and the periglomerular interstitium, in normal glomerular physiology. A more important reason has been the lack of an established primary role for the parietal epithelium in glomerular diseases. However, in recent years, several studies have demonstrated that PECs are involved in extracapillary proliferation. In addition, PECs can become highly active, proliferating cells, expressing many growth factors, chemokines, cytokines, and their receptors. It was recently demonstrated that PECs also play a part in the development of focal segmental glomerulosclerosis (FSGS). This review summarises current knowledge of the PEC, with emphasis on the role of PECs in the development of FSGS. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Functional Adult Myocardium in the Absence of Na+-Ca2+ Exchange: Cardiac-Specific Knockout of NCX1

The excitation–contraction coupling cycle in cardiac muscle is initiated by an influx of Ca2+ through voltage-dependent Ca2+ channels. Ca2+ influx induces a release of Ca2+ from the sarcoplasmic reticulum and myocyte contraction. To maintain Ca2+ homeostasis, Ca2+ entry is balanced by efflux mediated by the sarcolemmal Na+-Ca2+ exchanger. In the absence of Na+-Ca2+ exchange, it would be expected that cardiac myocytes would overload with Ca2+. Using Cre/loxP technology, we generated mice with a cardiac-specific knockout of the Na+-Ca2+ exchanger, NCX1. The exchanger is completely ablated in 80% to 90% of the cardiomyocytes as determined by immunoblot, immunofluorescence, and exchange function. Surprisingly, the NCX1 knockout mice live to adulthood with only modestly reduced cardiac function as assessed by echocardiography. At 7.5 weeks of age, measures of contractility are decreased by 20% to 30%. We detect no adaptation of the myocardium to the absence of the Na+-Ca2+ exchanger as measured by both immunoblots and microarray analysis. Ca2+ transients of isolated myocytes from knockout mice display normal magnitudes and relaxation kinetics and normal responses to isoproterenol. Under voltage clamp conditions, the current through L-type Ca2+ channels is reduced by 50%, although the number of channels is unchanged. An abbreviated action potential may further reduce Ca2+ influx. Rather than upregulate other Ca2+ efflux mechanisms, the myocardium appears to functionally adapt to the absence of the Na+-Ca2+ exchanger by limiting Ca2+ influx. The magnitude of Ca2+ transients appears to be maintained by an increased gain of sarcoplasmic reticular Ca2+ release. The myocardium of the NCX1 knockout mice undergoes a remarkable adaptation to maintain near normal cardiac function.
Effects of Obstructive Sleep Apnea and Gastroesophageal Reflux Disease on Asthma Control in Obesity

Background. Obesity is a risk factor for asthma. Obese asthmatics often have poor asthma control and respond poorly to therapy. It has been suggested that co-morbidities associated with obesity, such as reflux and obstructive sleep apnea, could be important factors contributing to poor asthma control in obese patients. Objectives. The purpose of this study was to determine if (1) reflux and/or (2) symptoms of sleep apnea contribute to poor asthma control in obesity. Methods. We studied asthmatic subjects participating in a trial of reflux treatment. Participants underwent baseline evaluation of asthma symptoms and lung function. Overall 304 participants underwent esophageal pH probe testing; 246 participants were evaluated for obstructive sleep apnea symptoms. Results. Of 402 participants in this trial, 51% were obese. Role of reflux in asthma control. Those with higher body mass index (BMI) reported a higher prevalence of reflux symptoms, but the prevalence of pH probe acid reflux was similar in all groups. Reflux was not associated with measures of asthma control in obese patients. Role of obstructive sleep apnea in asthma control. Symptoms and self-report of obstructive sleep apnea were more common with increasing BMI and associated with worse asthma control as measured by the Juniper Asthma Control questionnaire and Asthma Symptom Utility Index. Conclusions. Our data suggest that obstructive sleep apnea, but not gastroesophageal reflux disease, may contribute significantly to poor asthma control in obese patients.