Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of Cellular Metabolism by Protein Lysine Acetylation

Metabolic Regulation Through Acetylation Covalent modification of lysine residues in various proteins in the nucleus is a recognized mechanism for control of transcription. Now two papers suggest that acetylation may represent an important regulatory mechanism controlling the function of metabolic enzymes (see the Perspective by Norvell and McMahon). Zhao et al. (p. 1000) found that a large proportion of enzymes in various metabolic pathways were acetylated in human liver cells. Acetylation regulated various enzymes by distinct mechanisms, directly activating some, inhibiting one, and controlling the stability of another. Control of metabolism by acetylation appears to be evolutionarily conserved: Wang et al. (p. 1004) found that the ability of the bacterium Salmonella entericum to optimize growth on distinct carbon sources required differential acetylation of key metabolic enzymes, thus controlling flux through metabolic pathways. Regulation of enzymes by acetylation controls metabolic function in human liver cells. Protein lysine acetylation has emerged as a key posttranslational modification in cellular regulation, in particular through the modification of histones and nuclear transcription regulators. We show that lysine acetylation is a prevalent modification in enzymes that catalyze intermediate metabolism. Virtually every enzyme in glycolysis, gluconeogenesis, the tricarboxylic acid (TCA) cycle, the urea cycle, fatty acid metabolism, and glycogen metabolism was found to be acetylated in human liver tissue. The concentration of metabolic fuels, such as glucose, amino acids, and fatty acids, influenced the acetylation status of metabolic enzymes. Acetylation activated enoyl–coenzyme A hydratase/3-hydroxyacyl–coenzyme A dehydrogenase in fatty acid oxidation and malate dehydrogenase in the TCA cycle, inhibited argininosuccinate lyase in the urea cycle, and destabilized phosphoenolpyruvate carboxykinase in gluconeogenesis. Our study reveals that acetylation plays a major role in metabolic regulation.
Smallest Algae Thrive As the Arctic Ocean Freshens

In the Arctic Ocean, phytoplankton cell sizes have decreased with warming temperatures and fresher surface waters. As climate changes and the upper Arctic Ocean receives more heat and fresh water, it becomes more difficult for mixing processes to deliver nutrients from depth to the surface for phytoplankton growth. Competitive advantage will presumably accrue to small cells because they are more effective in acquiring nutrients and less susceptible to gravitational settling than large cells. Since 2004, we have discerned an increase in the smallest algae and bacteria along with a concomitant decrease in somewhat larger algae. If this trend toward a community of smaller cells is sustained, it may lead to reduced biological production at higher trophic levels.
Low-Cost Travel in Neurons

More precise measurements are now available for energy budgets in the brain. About 20% of the energy consumed by the body sustains brain function (1), yet the brain represents only 2% of human body mass. This consumption, reflected by the use of glucose and oxygen delivered by blood flow, provides signals that can be detected in real time with imaging techniques such as positron emission tomography and functional magnetic resonance imaging (2). On page 1405 of this issue, Alle et al. (3) weigh in on the ongoing debate about how energy utilization by brain neurons contributes to the signals detected by these techniques.
Targeted 3′ Processing of Antisense Transcripts Triggers Arabidopsis FLC Chromatin Silencing

Flowery Regulator Control of gene transcription is multilayered, depending on transcription factors, epigenetic mechanisms, and interactions with small RNA molecules. Liu et al. (p. 94, published online 3 December) have now found that for the FLOWERING LOCUS C (FLC) gene of the plant Arabidopsis, a backwards transcript of the gene conspires with 3′ RNA-processing tools and histone demethylation to regulate the transcription of the protein-coding gene. The 3′-processing events require the antisense, not the sense, RNA transcript. It is then the sense transcript that, in the end, regulates onset of flowering. A backward transcript of the FLOWERING LOCUS C gene of Arabidopsis is involved in regulation of the sense-strand transcription. Noncoding RNA is emerging as an important regulator of gene expression in many organisms. We are characterizing RNA-mediated chromatin silencing of the Arabidopsis major floral repressor gene, FLC. Through suppressor mutagenesis, we identify a requirement for CstF64 and CstF77, two conserved RNA 3′-end–processing factors, in FLC silencing. However, FLC sense transcript 3′ processing is not affected in the mutants. Instead, CstF64 and CstF77 are required for 3′ processing of FLC antisense transcripts. A specific RNA-binding protein directs their activity to a proximal antisense polyadenylation site. This targeted processing triggers localized histone demethylase activity and results in reduced FLC sense transcription. Targeted 3′ processing of antisense transcripts may be a common mechanism triggering transcriptional silencing of the corresponding sense gene.
Positron emission tomography imaging of serotonin transporters in the human brain using [11C](+)McN5652

This paper presents the first Positron Emission Tomography (PET) images of the serotonin (5‐hydroxytryptamine, 5‐HT) transporter in the living human brain. PET imaging was performed in three healthy subjects after administration of [11C](+)McN5652 (the (+) enantiomer of trans‐l,2,3,5,6,10β‐hexahydro‐6‐[4‐(methylthio) phenyl]pyrrolo‐[2,1‐a] ‐isoquinoline), a radioligand previously shown to selectively label the 5‐HT transporter in vivo in the mammalian (mouse and baboon) brain. To demonstrate the specificity of [11C](+)McN5652 binding, additional images were obtained in the same subjects after injection of [11C](−)McN5652, the pharmacologically inactive enantiomer, and, in two of the subjects, with [11C](+)McN5652 after pretreatment with the 5‐HT uptake site blocker fluoxetine.
Functional Outcome of Arthroscopic Repair with Concomitant Manipulation in Rotator Cuff Tears with Stiff Shoulder

Background Little has been reported on treatment of rotator cuff tears with shoulder stiffness. Hypothesis Rotator cuff tears with shoulder stiffness will show worse clinical results than will tears without stiffness. Those with stiffness are expected to take longer time in pain reduction and recovery of range of motion. Study Design Case control study; Level of evidence, 3. Methods Among patients who underwent arthroscopic rotator cuff repairs, 15 cases with preoperative shoulder stiffness (group A) and 30 without shoulder stiffness (group B) were enrolled in this study. Preoperative mean forward flexion was 118.3° in group A and 163.4° in group B, whereas external rotation at the side was 34.6° and 55.0°, respectively. The mean follow-up period of group A was 29.8 months (range, 19.5-73.9 months) and 32.4 months (range, 16–0.6 months) in group B. Results The mean visual analog scale during motion at the last follow-up was 0.75 in group A and 0.76 in group B (P = .942). The mean University of California at Los Angeles score was, respectively, 33.1 and 33.2 points (P = .561). Forward flexion was 166.7° in group A and 170.2° in group B, whereas external rotation at the side was 48.8° and 53.4°, respectively (P = .157 and .384, respectively). However, the 2 groups showed a significant difference in forward flexion until 1 year postoperatively as group A recovered more slowly (P = .021). Both groups showed significant differences in external rotation at the side, internal rotation to the back, and cross-body adduction until 6 weeks postoperatively (P = .009, P < .001, and P = .026, respectively). Conclusion Pain, range of motion, muscle strength, and function all significantly improved after arthroscopic rotator cuff repair, regardless of the presence of shoulder stiffness. Patients with full-thickness rotator cuff tears and stiffness of the shoulder can be treated with a single surgery and concomitant manipulation with overall good results. Although final outcomes were as good as those in patients without stiffness, the return of range of motion took longer in those patients undergoing manipulation for stiffness of the shoulder.
Individual Skill Progression on a Virtual Reality Simulator for Shoulder Arthroscopy

Background Previous studies have demonstrated a correlation between surgical experience and performance on a virtual reality arthroscopy simulator but only provided single time point evaluations. Additional longitudinal studies are necessary to confirm the validity of virtual reality simulation before these teaching aids can be more fully recommended for surgical education. Hypothesis Subjects will show improved performance on simulator retesting several years after an initial baseline evaluation, commensurate with their advanced surgical experience. Study Design Controlled laboratory study. Methods After gaining further arthroscopic experience, 10 orthopaedic residents underwent retesting 3 years after initial evaluation on a Procedicus virtual reality arthroscopy simulator. Using a paired t test, simulator parameters were compared in each subject before and after additional arthroscopic experience. Subjects were evaluated for time to completion, number of probe collisions with the tissues, average probe velocity, and distance traveled with the tip of the simulated probe compared to an optimal computer-determined distance. In addition, to evaluate consistency of simulator performance, results were compared to historical controls of equal experience. Results Subjects improved significantly (P < .02 for all) in the 4 simulator parameters: completion time (−51 %), probe collisions (−29%), average velocity (+122%), and distance traveled (−;32%). With the exception of probe velocity, there were no significant differences between the performance of this group and that of a historical group with equal experience, indicating that groups with similar arthroscopic experience consistently demonstrate equivalent scores on the simulator. Conclusion Subjects significantly improved their performance on simulator retesting 3 years after initial evaluation. Additionally, across independent groups with equivalent surgical experience, similar performance can be expected on simulator parameters; thus it may eventually be possible to establish simulator benchmarks to indicate likely arthroscopic skill. Clinical Relevance These results further validate the use of surgical simulation as an important tool for the evaluation of surgical skills.
Topical Glyceryl Trinitrate and Noninsertional Achilles Tendinopathy

Background Topical glyceryl trinitrate (GTN) therapy has been advocated in the treatment of Achilles tendinopathy. The mechanism of action is unknown but may be related to modulation of local nitric oxide levels. Hypothesis Topical GTN therapy for noninsertional Achilles tendinopathy will significantly enhance clinical improvement and will be associated with increased collagen synthesis within the tendon. Study Design Randomized controlled clinical trial; Level of evidence, 1. Methods Forty patients were recruited. Twenty underwent standard nonoperative physical therapy, and 20 underwent physical therapy and topical GTN daily. Clinical outcome was assessed using the Ankle Osteoarthritis Scale (AOS) visual analog score. Patients who failed to improve with conservative measures and who underwent surgical decompression had histological and immunohistochemical examination of samples from the Achilles tendon. Results Glyceryl trinitrate did not offer any additional clinical benefit over standard nonoperative treatment for noninsertional Achilles tendinopathy. After 6 months of treatment, there was no significant difference in scores between the groups for pain (3.0 vs 3.1, P = .42) or disability (2.15 vs 2.25, P = .38). Histological examination did not show any difference in neovascularization, collagen synthesis, or stimulated fibroblasts between the 2 groups. There was no evidence of modulation of nitric oxide synthase, a marker of nitric oxide production, in those tendons treated with GTN. Conclusion and Clinical Relevance This study has failed to support the clinical benefit of GTN patches previously described in the literature. In the available tissue samples, there did not appear to be any histological or immunohistochemical change in Achilles tendinopathy treated with GTN compared with those undergoing standard nonoperative therapy.
Tibiofemoral Contact Pressures and Osteochondral Microtrauma during Anterior Cruciate Ligament Rupture Due to Excessive Compressive Loading and Internal Torque of the Human Knee

Background The knee is one of the most frequently injured joints, including 80 000 anterior cruciate ligament (ACL) tears in the United States each year. Bone bruises are seen in over 80% of patients with ACL injuries, and have been associated with an overt loss of cartilage overlying those regions within 6 months of injury. Hypothesis The level of contact pressure developed in the human knee joint and the extent of articular cartilage and underlying subchondral bone injuries will depend on the mechanism of applied loads/moments during rupture of the ACL. Study Design Controlled laboratory study. Methods Seven knee pairs, flexed to 30°, were loaded in compression or internal torsion until injury. Pressure-sensitive film recorded the magnitude and location of contact. Histologic analysis and magnetic resonance imaging were used to document microtrauma to the tibial plateau cartilage and subchondral bone. Results All specimens suffered ACL injury, either in the form of a midsubstance rupture or avulsion fracture. The contact area and pressures were higher for compression than torsion experiments. After being loaded, the articular cartilage in the central and posterior regions of the medial tibial plateau showed increased magnetic resonance imaging signal intensity, corresponding to an increased susceptibility to absorb water. Histologically, there were more microcracks in the subchondral bone and more articular cartilage damage in the compression than torsion experiments. Conclusion Significant damage occurs to the articular cartilage and underlying subchondral bone during rupture of the ACL. The types and extent of these tissue injuries are a function of the mechanism of ACL rupture. Clinical Relevance Patients suffering an ACL injury may be at risk of osteochondral damage, especially if the mechanism of injury involves a high compressive loading component, such as during a jump landing.
The Epidemiology of United States High School Soccer Injuries, 2005–2007

Background United States high school soccer participation increased 5 fold over the last 30 years. With increased participation comes increased injury incidence. Hypothesis High school soccer injury patterns will vary by gender and type of exposure. Study Design Descriptive epidemiologic study. Methods Soccer-related injury data were collected over the 2005–2006 and 2006–2007 school years from 100 nationally representative United States high schools via Reporting Information Online (RIO, an Internet-based sports-related injury surveillance system). Results Participating certified athletic trainers reported 1524 soccer injuries during 637 446 athlete exposures (AEs), for an injury rate of 2.39 per 1000 AEs, corresponding to a nationally estimated 807 492 soccer-related injuries during the 2005–2006 and 2006–2007 seasons. The injury rate per 1000 AEs was greater during competition (4.77) than practice (1.37) (rate ratio [RR] = 3.49; 95% confidence interval [CI], 3.15–3.87). Overall, the most frequent diagnoses were incomplete ligament sprains (26.8%), incomplete muscle strains (17.9%), contusions (13.8%), and concussions (10.8%). The most commonly injured body sites were the ankle (23.4%), knee (18.7%), head/face (13.7%), and thigh/upper leg (13.1%). Similar proportions of boys (57.9%) and girls (53.9%) returned to activity in <1 week. During competition, girls sustained complete knee ligament sprains requiring surgery at a rate of 26.4 per 100 000 AEs, higher than the rate among boys during competition (1.98 per 100 000 AEs) (RR = 13.3; 95% CI, 3.15–56.35) and among girls during practice (2.34 per 100 000 AEs) (RR = 11.3; 95% CI, 4.31–29.58). Player-to-player contact was more common among competition injuries (injury proportion ratio [IPR] = 2.42; 95% CI, 2.01–2.92), while noncontact mechanisms were more common among practice injuries (IPR = 2.39; 95% CI, 1.90–3.01). Conclusions High school soccer injury patterns vary by gender and type of exposure. Identifying such differences in injury patterns is the important first step in the development of evidence-based, targeted injury prevention efforts.
Variety—the Splice of Life—in Microbial Communities

Splicing of viral fragments into bacterial and archaeal genomes may provide protection against viral predation. Bacteria and Archaea are commonly thought to exist as clonal populations because they reproduce asexually. However, genomic studies have shown that the evolutionary trajectories of most bacterial and archaeal populations are profoundly modified by exchange of genetic information, which creates natural populations that are inherently diverse. Much of this genomic variation confers no selective advantage or leads to evolutionary dead ends, some provides the raw material for selection that gives rise to new capabilities and lineages, and some may be critically involved in defense against mobile elements. Recently, it has become apparent that many Bacteria and Archaea splice into their genomes tiny fragments from the viruses and other mobile elements that harness them to replicate and survive. The uptake of these fragments can be so rapid that most bacterial and archaeal cells in a single population could be genomically distinct at the hypervariable locus where fragment insertion occurs. Variety that results from this diversification process could, in some cases, be critical to host population survival.
The Speaking Brain

Recordings of electrical activity in the human brain reveal the fine-tuned, stepwise neuronal processing of language and speech. How does intention to speak become the action of speaking? It involves the generation of a preverbal message that is tailored to the requirements of a particular language, and through a series of steps, the message is transformed into a linear sequence of speech sounds (1, 2). These steps include retrieving different kinds of information from memory (semantic, syntactic, and phonological), and combining them into larger structures, a process called unification. Despite general agreement about the steps that connect intention to articulation, there is no consensus about their temporal profile or the role of feedback from later steps (3, 4). In addition, since the discovery by the French physician Pierre Paul Broca (in 1865) of the role of the left inferior frontal cortex in speaking, relatively little progress has been made in understanding the neural infrastructure that supports speech production (5). One reason is that the characteristics of natural language are uniquely human, and thus the neurobiology of language lacks an adequate animal model. But on page 445 of this issue, Sahin et al. (6) demonstrate, by recording neuronal activity in the human brain, that different kinds of linguistic information are indeed sequentially processed within Broca's area.
Resonance Fluorescence of a Single Artificial Atom

Superconducting Quantum Optics The coherence properties of superconducting circuits enable them to be developed as qubits in quantum information processing applications. Astafiev et al. (p. 840) now show that these macroscopic superconducting devices also behave as artificial atoms and can exhibit quantum optical effects. The ability to fabricate and integrate these superconducting devices in electronic circuitry may help toward developing a fully controlled quantum optics system on a chip. A superconducting circuit can exhibit quantum optical behavior, acting like an artificial atom. An atom in open space can be detected by means of resonant absorption and reemission of electromagnetic waves, known as resonance fluorescence, which is a fundamental phenomenon of quantum optics. We report on the observation of scattering of propagating waves by a single artificial atom. The behavior of the artificial atom, a superconducting macroscopic two-level system, is in a quantitative agreement with the predictions of quantum optics for a pointlike scatterer interacting with the electromagnetic field in one-dimensional open space. The strong atom-field interaction as revealed in a high degree of extinction of propagating waves will allow applications of controllable artificial atoms in quantum optics and photonics.
Electromyographic Analysis of Forearm Muscles in Professional and Amateur Golfers

Background No fine-wire electromyography studies have been performed to compare the activity of forearm muscles in professional golfers versus amateur golfers. Hypothesis The fine-wire electromyographic activity of forearm muscles differs between professional and amateur golfers during the different phases of the golf swing. Study Design Controlled laboratory study. Methods Ten male right-handed amateur golfers and 10 male right-handed professional golfers without history of elbow symptoms were tested with fine-wire electromyographic electrodes inserted into the flexor carpi radialis, pronator teres, flexor carpi ulnaris, and extensor carpi radialis brevis muscles of both forearms. Electromyographic data were synchronized with video data, and the muscle activity was expressed as a percentage of maximum manual muscle test activity for each phase of the golf swing. Results Compared with professional golfers, amateur golfers had more muscle activity in the pronator teres of the trail arm (right arm in a right-handed golfer) in the forward swing phase (120.9% maximum manual muscle test vs 57.4% maximum manual muscle test; P =. 04) and a trend toward increased activity in the acceleration phase (104.8% maximum manual muscle test vs 53.1% maximum manual muscle test; P =. 08). In contrast, professional golfers had more muscle activity in the pronator teres of the lead arm (left arm in a right-handed golfer) in the acceleration phase (88.1% maximum manual muscle test vs 36.3% maximum manual muscle test; P =. 03) and a trend toward increased activity in the early follow-through phase (58.1% maximum manual muscle test vs 28.8% maximum manual muscle test; P =. 06). Conclusion Pronator teres muscle activity in the golf swing differs significantly between professional and amateur golfers. Clinical Relevance Exercises with an emphasis on stretching and strengthening of the pronator teres may be useful in treating and/or preventing medial epicondylitis in amateur golfers.