YAP charge patterning mediates signal integration through transcriptional co-condensates.

Transcription factor dynamics are used to selectively engage gene regulatory programs. Biomolecular condensates have emerged as an attractive signaling substrate in this process, but the underlying mechanisms are not well-understood. Here, we probed the molecular basis of YAP signal integration through transcriptional condensates. Leveraging light-sheet single-molecule imaging and synthetic condensates, we demonstrate charge-mediated co-condensation of the transcriptional regulators YAP and Mediator into transcriptionally active condensates in stem cells. IDR sequence analysis and YAP protein engineering demonstrate that instead of the net charge, YAP signaling specificity is established through its negative charge patterning that interacts with Mediator's positive charge blocks. The mutual enhancement of YAP/Mediator co-condensation is counteracted by negative feedback from transcription, driving an adaptive transcriptional response that is well-suited for decoding dynamic inputs. Our work reveals a molecular framework for YAP condensate formation and sheds new light on the function of YAP condensates for emergent gene regulatory behavior.

Proton-Coupled Electron Transfer on Cu2O/Ti3C2Tx MXene for Propane (C3H8) Synthesis from Electrochemical CO2 Reduction.

Electrochemical CO2 reduction reaction (CO2RR) to produce value-added multi-carbon chemicals has been an appealing approach to achieving environmentally friendly carbon neutrality in recent years. Despite extensive research focusing on the use of CO2 to produce high-value chemicals like high-energy-density hydrocarbons, there have been few reports on the production of propane (C3H8), which requires carbon chain elongation and protonation. A rationally designed 0D/2D hybrid Cu2O anchored-Ti3C2Tx MXene catalyst (Cu2O/MXene) is demonstrated with efficient CO2RR activity in an aqueous electrolyte to produce C3H8. As a result, a significantly high Faradaic efficiency (FE) of 3.3% is achieved for the synthesis of C3H8 via the CO2RR with Cu2O/MXene, which is ≈26 times higher than that of Cu/MXene prepared by the same hydrothermal process without NH4OH solution. Based on in-situ attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and density functional theory (DFT) calculations, it is proposed that the significant electrocatalytic conversion originated from the synergistic behavior of the Cu2O nanoparticles, which bound the *C2 intermediates, and the MXene that bound the *CO coupling to the C3 intermediate. The results disclose that the rationally designed MXene-based hybrid catalyst facilitates multi-carbon coupling as well as protonation, thereby manipulating the CO2RR pathway.

MYC phase separation selectively modulates the transcriptome.

Dysregulation and enhanced expression of MYC transcription factors (TFs) including MYC and MYCN contribute to the majority of human cancers. For example, MYCN is amplified up to several hundredfold in high-risk neuroblastoma. The resulting overexpression of N-myc aberrantly activates genes that are not activated at low N-myc levels and drives cell proliferation. Whether increasing N-myc levels simply mediates binding to lower-affinity binding sites in the genome or fundamentally changes the activation process remains unclear. One such activation mechanism that could become important above threshold levels of N-myc is the formation of aberrant transcriptional condensates through phase separation. Phase separation has recently been linked to transcriptional regulation, but the extent to which it contributes to gene activation remains an open question. Here we characterized the phase behavior of N-myc and showed that it can form dynamic condensates that have transcriptional hallmarks. We tested the role of phase separation in N-myc-regulated transcription by using a chemogenetic tool that allowed us to compare non-phase-separated and phase-separated conditions at equivalent N-myc levels, both of which showed a strong impact on gene expression compared to no N-myc expression. Interestingly, we discovered that only a small percentage (<3%) of N-myc-regulated genes is further modulated by phase separation but that these events include the activation of key oncogenes and the repression of tumor suppressors. Indeed, phase separation increases cell proliferation, corroborating the biological effects of the transcriptional changes. However, our results also show that >97% of N-myc-regulated genes are not affected by N-myc phase separation, demonstrating that soluble complexes of TFs with the transcriptional machinery are sufficient to activate transcription.

Age Group-Specific Improvement of Vertebral Scoliosis after the Surgical Release of Congenital Muscular Torticollis.

Background Congenital muscular torticollis (CMT) is a common musculoskeletal disorder in children. Secondary scoliosis can occur in patients with CMT; however, the extent of inclination and improvement of scoliosis after surgical correction of CMT have not been adequately studied. In this study, we aimed to evaluate and measure the improvement in vertebral tilting after surgical correction according to age at the time of surgery. Methods Between June 2007 and January 2020, 831 patients with CMT underwent sternocleidomastoid release. Among them, 426 patients were enrolled, and their medical records were retrospectively reviewed. Ultimately, 210 patients available for radiological evaluation and analysis were enrolled in this study. The patients were divided into four groups according to age at the time of surgery to determine the relationship between age and changes in scoliosis. Results Our findings showed an improvement in scoliosis in all age groups after surgery. The results for follow-up after 1 year confirmed long-term improvement in vertebral tilting. The degree of improvement in scoliosis was significantly higher in the younger age group than in patients aged 18 years or older. Conclusion The effect of surgical release on scoliosis was significant in all age groups. The findings of this study suggest that CMT should be corrected before the age of 3 years to ensure an optimal surgical mitigation of scoliosis. Furthermore, in cases of neglected CMT, surgical release should be actively attempted because there is significant improvement.

Phase separation of YAP-MAML2 differentially regulates the transcriptome.

Phase separation (PS) drives the formation of biomolecular condensates that are emerging biological structures involved in diverse cellular processes. Recent studies have unveiled PS-induced formation of several transcriptional factor (TF) condensates that are transcriptionally active, but how strongly PS promotes gene activation remains unclear. Here, we show that the oncogenic TF fusion Yes-associated protein 1-Mastermind like transcriptional coactivator 2 (YAP-MAML2) undergoes PS and forms liquid-like condensates that bear the hallmarks of transcriptional activity. Furthermore, we examined the contribution of PS to YAP-MAML2-mediated gene expression by developing a chemogenetic tool that dissolves TF condensates, allowing us to compare phase-separated and non-phase-separated conditions at identical YAP-MAML2 protein levels. We found that a small fraction of YAP-MAML2-regulated genes is further affected by PS, which include the canonical YAP target genes CTGF and CYR61, and other oncogenes. On the other hand, majority of YAP-MAML2-regulated genes are not affected by PS, highlighting that transcription can be activated effectively by diffuse complexes of TFs with the transcriptional machinery. Our work opens new directions in understanding the role of PS in selective modulation of gene expression, suggesting differential roles of PS in biological processes.

Cement/Sulfur for Lithium-Sulfur Cells.

Lithium-sulfur batteries represent a promising class of next-generation rechargeable energy storage technologies, primarily because of their high-capacity sulfur cathode, reversible battery chemistry, low toxicity, and cost-effectiveness. However, they lack a tailored cell material and configuration for enhancing their high electrochemical utilization and stability. This study introduces a cross-disciplinary concept involving cost-efficient cement and sulfur to prepare a cement/sulfur energy storage material. Although cement has low conductivity and porosity, our findings demonstrate that its robust polysulfide adsorption capability is beneficial in the design of a cathode composite. The cathode composite attains enhanced cell fabrication parameters, featuring a high sulfur content and loading of 80 wt% and 6.4 mg cm-2, respectively. The resulting cell with the cement/sulfur cathode composite exhibits high active-material retention and utilization, resulting in a high charge storage capacity of 1189 mA∙h g-1, high rate performance across C/20 to C/3 rates, and an extended lifespan of 200 cycles. These attributes contribute to excellent cell performance values, demonstrating areal capacities ranging from 4.59 to 7.61 mA∙h cm-2, an energy density spanning 9.63 to 15.98 mW∙h cm-2, and gravimetric capacities between 573 and 951 mA∙h g-1 per electrode. Therefore, this study pioneers a new approach in lithium-sulfur battery research, opting for a nonporous material with robust polysulfide adsorption capabilities, namely cement. It effectively showcases the potential of the resulting cement/sulfur cathode composite to enhance fabrication feasibility, cell fabrication parameters, and cell performance values.

Comparing the Pericapsular Nerve Group Block and the Lumbar Plexus Block for Hip Fracture Surgery: A Single-Center Randomized Double-Blinded Study.

Lumbar plexus blocks (LPBs) are routinely employed for analgesia in hip fracture surgery; however, a novel regional technique, the pericapsular nerve group (PENG) block, potentially offers comparable pain reduction while preserving motor function. Patients aged 45-90 years who underwent hip fracture surgery were allocated to receive either a PENG block or an LPB for analgesia. The primary outcome was the incidence of quadriceps motor block (defined as the paresis or paralysis of the knee extension) at 12 h postoperatively. The secondary outcomes included the performance time, the time to first analgesic requirement, postoperative intravenous (IV) fentanyl consumption, the ability to undergo physiotherapy at 24 and 48 h, complications, sensory and motor block assessments, postoperative numeric rating scale (NRS) pain scores, and patient outcome questionnaires. There was a significantly lower incidence of quadriceps motor block at 6 h (26.7% vs. 80.0%; p < 0.001) and at 12 h (20.0% vs. 56.7%; p = 0.010). The PENG block provided better preservation of the sensory block as well as better performance time (p < 0.001) and time to first analgesia requirement (p = 0.034), whereas the LPB resulted in lower postoperative IV fentanyl consumption at 24 h (p = 0.013). The PENG block demonstrated superiority over the LPB in preserving quadriceps strength and patient satisfaction without any substantial complications, despite higher opioid consumption within the first 24 h post-surgery.

How well does societal mobility restriction help control the COVID-19 pandemic? Evidence from real-time evaluation

ObjectivesTo determine the impact of restrictions on mobility on reducing transmission of COVID-19. DesignDaily incidence rates lagged by 14 days were regressed on mobility changes using LOESS regression and logit regression between the day of the 100th case in each country to August 31, 2020. Setting34 OECD countries plus Singapore and Taiwan. ParticipantsGoogle mobility data were obtained from people who turned on mobile device-based global positioning system (GPS) and agreed to share their anonymized position information with Google. InterventionsWe examined the association of COVID-19 incidence rates with mobility changes, defined as changes in categories of domestic location, against a pre-pandemic baseline, using country-specific daily incidence data on newly confirmed COVID-19 cases and mobility data. ResultsIn two thirds of examined countries, reductions of up to 40% in commuting mobility (to workplaces, transit stations, retailers, and recreation) were associated with decreased COVID-19 incidence, more so early in the pandemic. However, these decreases plateaued as mobility remained low or decreased further. We found smaller or negligible associations between mobility restriction and incidence rates in the late phase in most countries. ConclusionMild to moderate degrees of mobility restriction in most countries were associated with reduced incidence rates of COVID-19 that appear to attenuate over time, while some countries exhibited no effect of such restrictions. More detailed research is needed to precisely understand the benefits and limitations of mobility restrictions as part of the public health response to the COVID-19 pandemic. WHAT IS ALREADY KNOWN ON THIS TOPICSince SARS-CoV-2 became a pandemic, restrictions on mobility such as limitations on travel and closure of offices, restaurants, and shops have been imposed in an unprecedented way in both scale and scope to prevent the spread of COVID-19 in the absence of effective treatment options or a vaccine. Although mobility restriction has also brought about tremendous costs such as negative economic growth and other collateral impacts on health such as increased morbidity and mortality from lack of access to other essential health services, little evidence exists on the effectiveness of mobility restriction for the prevention of disease transmission. A search of PUBMED and Google Scholar for publications on this topic through Sep 20, 2020 revealed that most of the evidence on the effectiveness of physical distancing comes from mathematical modeling studies using a variety of assumptions. One study investigated only the combined effect of several interventions, including physical distancing, among SARS-CoV-2 infected patients. WHAT THIS STUDY ADDSThis is the first study to investigate the association between change in mobility and incidence of COVID-19 globally using real-time measures of mobility at the population level. For this, we used Google Global Mobility data and the daily incidence of COVID-19 for 36 countries from the day of 100th case detection through August 31, 2020. Our findings from LOESS regression show that in two-thirds of countries, reductions of up to 40% in commuting mobility were associated with decreased COVID-19 incidence, more so early in the pandemic. This decrease, however, plateaued as mobility decreased further. We found that associations between mobility restriction and incidence became smaller or negligible in the late phase of the pandemic in most countries. The reduced incidence rate of COVID-19 cases with a mild to moderate degree of mobility restriction in most countries suggests some value to limited mobility restriction in early phases of epidemic mitigation. The lack of impact in some others, however, suggests further research is needed to confirm these findings and determine the distinguishing factors for when mobility restrictions are helpful in decreasing viral transmission. Governments should carefully consider the level and period of mobility restriction necessary to achieve the desired benefits and minimize harm.

The evolving role of the community pharmacist in chronic disease management - a literature review

<p><b>INTRODUCTION</b>We appraised the roles and responsibilities assigned to community pharmacists internationally and in Singapore.</p><p><b>MATERIALS AND METHODS</b>A systematic search of international peer-reviewed literature was undertaken using Medline. Grey literature was identified through generic search engines. The search period was from 1 January 1991 to 30 July 2009. The search criteria were English language manuscripts and search terms "community pharmacist", "community pharmacy", "disease management" and "roles" as a major heading. Boolean operators were used to combine the search terms. Identified abstracts were independently reviewed and the findings were presented as a narrative summary.</p><p><b>RESULTS</b>Overall, we reviewed 115 articles on an abstract level and retrieved 45 of those as full text articles for background information review and inclusion into the evidence report. Of the articles included in the review, 32% were from United Kingdom (UK). Literature highlights the multi-faceted role of the community pharmacist in disease management. Community pharmacists were involved in the management of asthma, arthritis, cardiovascular diseases, diabetes, depression, hypertension, osteoporosis and palliative care either alone or in the disease management team. Evidence of effectiveness for community pharmacy/ community pharmacist interventions exists for lipid, diabetes, and hypertension management and for preventive services such as weight management, osteoporosis prevention and fl u immunisation services. Majority of the community pharmacists in Singapore play the traditional role of dispensing. Attempts by the private community pharmacies to provide some professional services were not successful due to lack of funding. Factors found to impede the growth of community pharmacists are insufficient integration of community pharmacist input into healthcare pathways, poor relationship among pharmacists and physicians, lack of access to patient information, time constraints and inadequate compensation.</p><p><b>CONCLUSION</b>Evidence from observational studies points out the wide range of roles played by the community pharmacist and provides insights into their integration into chronic disease management programmes and health promotion.</p>

Clinical Observation of Testicular Tumors / 대한비뇨기과학회지

Clinical observation of testicular tumors was made on 10 cases who were admitted to the Department of Urology, Seoul Adventist Hospita1, during the period from January 1975 to June 1979. The results are summarized as follows : l. During this period, the total number of male in-patients was 496 among which 10 cases had testicular tumor, giving a rate of 2.02% 2. Among 74 cases of male genitourinary tract tumor, there were 10 cases of testicular tumor with a rate of 13.51%. 3. Age distribution was between 5 months and 55 years, showing the highest incidence in the 30 to 39 year age range (30.0%). 4. There were 6 cases (60.0%) on the right. 4 cases (40.0%) on the left. 5. 70.0% of the cases visited the hospital within 6 months after onset of the symptoms. 6. The frequent subjective symptoms were as follows: painless scrotal mass in 80.0%, painful scrotal mass in 20.0%, palpable abdominal mass in l0.0% and lumbar back pain in 10.0% as well as other symptoms. 7. There were 2 cases (20.0%) with metastasis on admission: l case in inguinal lymph node and 1 case in lung and lumbar lymph node. 8. There were 3 cases of seminoma (30.0%) including 2 cases combined with teratoma and embryonal carcinoma respectively, 2 cases of yolk sac tumor (20.0%), 2 cases of teratocarcinoma (20.0%), 2 cases of teratoma (20.0%) and 1 cases of metastatic adenocarcinoma from stomach (10.0%) 9. These patient were managed by surgery and/or irradiation and/or chemotherapy.

A Case of Sparganosis in the Left Flank and the Left Scrotum / 대한비뇨기과학회지

The human sparganum mansoni infestation was reported 63 cases in Korea until 1974, but urogenital infestation of sparganum is relatively rare. We experienced a case of sparganosis in which one parasite migrated from the Left flank to the left scrotum and the other remained in the left flank. The white ribbon worm-like structure was crawling in the subcutaneous tissue of the left scrotum. This 51 year lod male patient had an episode of intake of raw snake as a tonic 2 year ago in Kyungki-do, Korea.

Clinical Observation of Renal Tuberculosis / 대한비뇨기과학회지

Clinical observation of renal tuberculosis was made on 44 cases who were admitted to the Department of Urology. Seoul Adventist Hospital, during the period from January 1973 to December 1978. The results are summarized as follows: 1. During this period, the total number of in-patients was 782 among which 44 cases had renal tuberculosis. giving a rate of 5.6% of total in-patients. The ratio of the annual number of renal tuberculosis cases against total number of urologic in-patients is decreasing significantly. 2. 24 cases (54.5%= out of 44, were in the age group of 21 to 40, and male to female ratio was 1.6: 1. 3. Both kidneys were affected in 21 cases (47.8%), while l3 cases (29.5%) involved the left kidney and 10 cases (22.7%) the right one. 4. The frequent subjective complaints were as Follows: Frequency in 70.5%, gross total hematuria in 68.2%, painful urination in 56.8% and flank pain or dullness in 52.3%. 5. 43.2% of the cases visited the hospital within 6 months after onset of the symptoms. 6. 68.2% of the cases were associated with active or healed pulmonary tuberculosis. 7. Other presenting tuberculous lesions and combined diseases were as follows: Tuberculous epididymitis in 5 cases, tuberculous lymphadenitis in 3 cases, contracted bladder in 11 cases. Uremia in 4 cases and urinary stone in 3 cases. 8. Normal ranges of BUN and Creatinine were found in 34 cases and 37 cases respectively and in creased ESR was found in 28 cases. 9. Urinalysis findings revealed proteinuria in 72.7%, hematuria in 93.2% and pyuria in 84.1%. Urine AFB was found in 61.4% by Ziehl Neelsen`s method and in the 38.6% of negative stains, urine AFE culture revealed positive in 6.8%. 10. On the excretory urogram of 65 kidneys, functional changes are as follows. Nonvieualization in 41.6%, caliectasis in 3O.8%, hydrourettronephrosis in 23.6%. moth-eaten appear ance in 18.5% and contracted bladder in 25.0%. 11. Retrograde or antegrade pyelographic changes of the l9 non-visualized kidneys on excretory uro-gram are as follows: hydronephrosis in 52.6%, caliectasis in 36.8%, parenchymal destruction in 3l.6 % and cavity with pyonephrosis in 21.1%. l2. The patients were managed by chemotherapy only in 11 cases and combined chemotherapy and nephrectomy in 28 cases, nephrostomy in 13 cases and ileocystoplasty in 4 cases. 13. Histopathologic findings of 28 nephrectomized kidneys disclosed parenchymal tuberculous granulomas in all cases and severely atrophic changes in 1 cases.

A Case of Horseshoe Kidney with Multiple Renal Stones and Hydronephrosis / 대한비뇨기과학회지

Horseshoe kidney is a nonfatal anomaly of renal development characterized by fusion of one poles of both kidneys. Most clinical problems are caused by hydronephrosis and renal calculi. A case of horseshoe kidney with multiple renal stones and hydronephrosis in a 53 year-old woman is reported and literatures are reviewed. This case was diagnosed easily radiologically and treated successfully by pyelolithotomy & pyeloplasty.