Miracle-dz/UniFAR-FTUs huggingface dataset:
Questioning new answers regarding Holocene chicken domestication in China

Xiang et al. (1) assert that chickens were domesticated on the North China plain 10,000 y ago. Although a great deal remains unknown about the temporal and geographic origins of poultry husbandry, this claim is extraordinary. We welcome the increasing application of modern bioarcheological techniques to questions pertaining to animal domestication in China, but we are skeptical about these conclusions for several reasons.
Applications of nanotechnology in health care: Perspectives and opportunities

ABSTRACT Nanotechnology have huge potential in developing several drug delivery systems and also in various biomedical applications. Nanotechnology research is booming worldwide, having an impact on multiple sectors and with a general belief that medical and biological applications will form the greatest area of expansion over the next decade, driven by an attempt to bring radical solutions to areas of unmet medical needs. Applications of nanotechnology in medicine are especially promising, and areas such as disease diagnosis, drug targeting at specific sites in the body, and molecular imaging are being intensively investigated and some products are undergoing clinical trials. Different approaches like charged, gold and magnetic resonance nanoparticles show promise for drug delivery applications. Nanoparticulate drug delivery systems are extensively used to treat diseases of cardiovascular, lung, brain, cancer, etc.
Inactivation of EWS reduces PGC-1α protein stability and mitochondrial homeostasis

Significance Ewing sarcoma protein (EWS) is essential for various cellular processes but its role in energy metabolism has not been demonstrated. This study identifies a new role of EWS in mitochondria and cellular energy homeostasis. Loss of EWS leads to increased degradation of PGC-1α, a critical protein in maintaining mitochondrial function and energy metabolism. The increased degradation is due to an increased expression of FBXW7, a protein that promotes PGC-1α degradation. In mice lacking EWS, significant decreases in PGC-1α levels and in mitochondria number and function are observed in brown fat, skeletal muscles, and liver. A novel role in mitochondrial and energy homeostasis provides new insights into the expanding role of EWS and suggests an altered energy metabolism in tumors with EWS translocations. EWS (Ewing sarcoma) encodes an RNA/ssDNA binding protein that is frequently rearranged in a number of different cancers by chromosomal translocations. Physiologically, EWS has diverse and essential roles in various organ development and cellular processes. In this study, we uncovered a new role of EWS in mitochondrial homeostasis and energy metabolism. Loss of EWS leads to a significant decrease in mitochondria abundance and activity, which is caused by a rapid degradation of Peroxisome proliferator-activated receptor γ Coactivator (PGC-1α), a central regulator of mitochondria biogenesis, function, and cellular energy metabolism. EWS inactivation leads to increased ubiquitination and proteolysis of PGC-1α via proteasome pathway. Complementation of EWS in Ews-deficient cells restores PGC-1α and mitochondrial abundance. We found that expression of E3 ubiquitin ligase, FBXW7 (F-box/WD40 domain protein 7), is increased in the absence of Ews and depletion of Fbxw7 in Ews-null cells restores PGC-1α expression and mitochondrial density. Consistent with these findings, mitochondrial abundance and activity are significantly reduced in brown fat and skeletal muscles of Ews-deficient mice. Furthermore, expression of mitochondrial biogenesis, respiration and fatty acid β-oxidation genes is significantly reduced in the liver of Ews-null mice. These results demonstrate a novel role of EWS in mitochondrial and cellular energy homeostasis by controlling PGC-1α protein stability, and further implicate altered mitochondrial and energy metabolism in cancers harboring the EWS translocation.
Identification of a functional hotspot on ubiquitin required for stimulation of methyltransferase activity on chromatin

Significance This article applies a range of protein ligation methods at the level of chromatin to understand the cross-talk mechanism between the well-established biomedical target the human Dot1 (hDot1L) methyltransferase and the ubiquitylation of H2B at lysine 120. Through a systematic structure–activity relationship study of the ubiquitin surface in regard to hDot1L-mediated H3K79 methylation and further investigation with precisely engineered chromatin substrates, a functional hotspot within ubiquitin was identified that is essential to the stimulation of hDot1L activity. More broadly, this work shows how chemical synthesis approaches can be used to precisely tailor protein posttranslational modifications to afford mechanistic insights that would be impossible by other methods. Ubiquitylation of histone H2B at lysine 120 (H2B-Ub) plays a critical role in transcriptional elongation, chromatin conformation, as well as the regulation of specific histone H3 methylations. Herein, we report a strategy for the site-specific chemical attachment of ubiquitin to preassembled nucleosomes. This allowed expedited structure–activity studies into how H2B-Ub regulates H3K79 methylation by the methyltransferase human Dot1. Through an alanine scan of the ubiquitin surface, we identified a functional hotspot on ubiquitin that is required for the stimulation of human Dot1 in vitro. Importantly, this result was validated in chromatin from isolated nuclei by using a synthetic biology strategy that allowed selective incorporation of the hotspot-deficient ubiquitin mutant into H2B. The ubiquitin hotspot additionally impacted the regulation of ySet1-mediated H3K4 methylation but was not required for H2B-Ub–induced impairment of chromatin fiber compaction. These data demonstrate the utility of applying chemical ligation technologies to preassembled chromatin and delineate the multifunctionality of ubiquitin as a histone posttranslational modification.
Sodium Fluorescein Facilitates Guided Sampling of Diagnostic Tumor Tissue in Nonenhancing Gliomas

BACKGROUND Accurate tissue sampling in nonenhancing (NE) gliomas is a unique surgical challenge due to their intratumoral histological heterogeneity and absence of contrast enhancement as a guide for intraoperative stereotactic guidance. Instead, T2/fluid-attenuated inversion-recovery (FLAIR) hyperintensity on MRI is commonly used as an imaging surrogate for pathological tissue, but sampling from this region can yield nondiagnostic or underdiagnostic brain tissue. Sodium fluorescein is an intraoperative fluorescent dye that has a high predictive value for tumor identification in areas of contrast enhancement and NE in glioblastomas. However, the underlying histopathological alterations in fluorescent regions of NE gliomas remain undefined. OBJECTIVE To evaluate whether fluorescein can identify diagnostic tissue and differentiate regions with higher malignant potential during surgery for NE gliomas, thus improving sampling accuracy. METHODS Thirteen patients who presented with NE, T2/FLAIR hyperintense lesions suspicious for glioma received fluorescein (10%, 3 mg/kg intravenously) during surgical resection. RESULTS Patchy fluorescence was identified within the T2/FLAIR hyperintense area in 10 of 13 (77%) patients. Samples taken from fluorescent regions were more likely to demonstrate diagnostic glioma tissue and cytologic atypia (P < .05). Fluorescein demonstrated a 95% positive predictive value for the presence of diagnostic tissue. Samples from areas of fluorescence also demonstrated greater total cell density and higher Ki-67 labeling than nonfluorescent biopsies (P < .05). CONCLUSION Fluorescence in NE gliomas is highly predictive of diagnostic tumor tissue and regions of higher cell density and proliferative activity.
Enhancement of the Performance of Perovskite Solar Cells, LEDs, and Optical Amplifiers by Anti‐Solvent Additive Deposition

The efficiency of perovskite optoelectronic devices is increased by a novel method; its suitability for perovskite solar cells, light-emitting diodes, and optical amplifiers is demonstrated. The method is based on the introduction of organic additives during the anti-solvent step in the perovskite thin-film deposition process. Additives passivate grain boundaries reducing non-radiative recombination. The method can be easily extended to other additives.
The Introduction of Clinical Microsystems into an Emergency Department.

The provision of high quality care is the responsibility of all healthcare staff, but in today’s climate of ever decreasing budgets and resources it is even more important. The Emergency Medicine programme (EMP) has been charged by the Health Service Executive (HSE) to revolutionise the way emergency departments (ED) provide care in an effort to reduce the patient experience times in the ED. The overarching aim of the EMP is the provision of safe quality care , and one of the methodologies for achieving this aim is the use of systems management tools, the Emergency Medicine Programme recommends the use of Clinical Microsystems (microsystems).
Additive Manufacturing of Metal Structures at the Micrometer Scale

Currently, the focus of additive manufacturing (AM) is shifting from simple prototyping to actual production. One driving factor of this process is the ability of AM to build geometries that are not accessible by subtractive fabrication techniques. While these techniques often call for a geometry that is easiest to manufacture, AM enables the geometry required for best performance to be built by freeing the design process from restrictions imposed by traditional machining. At the micrometer scale, the design limitations of standard fabrication techniques are even more severe. Microscale AM thus holds great potential, as confirmed by the rapid success of commercial micro‐stereolithography tools as an enabling technology for a broad range of scientific applications. For metals, however, there is still no established AM solution at small scales. To tackle the limited resolution of standard metal AM methods (a few tens of micrometers at best), various new techniques aimed at the micrometer scale and below are presently under development. Here, we review these recent efforts. Specifically, we feature the techniques of direct ink writing, electrohydrodynamic printing, laser‐assisted electrophoretic deposition, laser‐induced forward transfer, local electroplating methods, laser‐induced photoreduction and focused electron or ion beam induced deposition. Although these methods have proven to facilitate the AM of metals with feature sizes in the range of 0.1–10 µm, they are still in a prototype stage and their potential is not fully explored yet. For instance, comprehensive studies of material availability and material properties are often lacking, yet compulsory for actual applications. We address these items while critically discussing and comparing the potential of current microscale metal AM techniques.
MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome

Significance Decades of research have not deciphered the mechanism by which methyl-CpG binding protein 2 (MeCP2) regulates transcription and why Rett symptoms manifest 1 to 2 y after birth. We hypothesized that the temporal dynamics of MeCP2 binding might provide an answer. We developed mice with an EGFP-tagged MeCP2 allele to identify high-resolution MeCP2 binding profiles in the adult mouse brain. Using genomic binding profiles, methylation maps, and mRNA deep-sequencing data, we found MeCP2 binds to non-CG methylation (mCH, not mCG) to regulate expression of genes altered in mouse models of MeCP2 disorders. These data and the parallel timing of mCH and MeCP2 postnatal accumulation suggest MeCP2 binds mCH as neurons mature to regulate gene expression, offering an explanation for the delayed onset of Rett. Epigenetic mechanisms, such as DNA methylation, regulate transcriptional programs to afford the genome flexibility in responding to developmental and environmental cues in health and disease. A prime example involving epigenetic dysfunction is the postnatal neurodevelopmental disorder Rett syndrome (RTT), which is caused by mutations in the gene encoding methyl-CpG binding protein 2 (MeCP2). Despite decades of research, it remains unclear how MeCP2 regulates transcription or why RTT features appear 6–18 months after birth. Here we report integrated analyses of genomic binding of MeCP2, gene-expression data, and patterns of DNA methylation. In addition to the expected high-affinity binding to methylated cytosine in the CG context (mCG), we find a distinct epigenetic pattern of substantial MeCP2 binding to methylated cytosine in the non-CG context (mCH, where H = A, C, or T) in the adult brain. Unexpectedly, we discovered that genes that acquire elevated mCH after birth become preferentially misregulated in mouse models of MeCP2 disorders, suggesting that MeCP2 binding at mCH loci is key for regulating neuronal gene expression in vivo. This pattern is unique to the maturing and adult nervous system, as it requires the increase in mCH after birth to guide differential MeCP2 binding among mCG, mCH, and nonmethylated DNA elements. Notably, MeCP2 binds mCH with higher affinity than nonmethylated identical DNA sequences to influence the level of Bdnf, a gene implicated in the pathophysiology of RTT. This study thus provides insight into the molecular mechanism governing MeCP2 targeting and sheds light on the delayed onset of RTT symptoms.
Genomic alterations in BCL2L1 and DLC1 contribute to drug sensitivity in gastric cancer

Significance Gastric cancer (GC) is one of the major causes of cancer-related deaths worldwide, but targeted therapy for GC is limited. Here, we identified two druggable targets from genomic alteration profiling of 103 patients with GC from Asia and validated the target suitability using patient-derived GC xenograft models, which recapitulate the tumor biology observed in patients. Combination therapy of irinotecan (standard treatment) with a BCL2L1 (BCL2-like 1)-targeted drug was effective in size reduction of GC tumors having amplification of the BCL2L1 gene, and genomic mutations of deleted in liver cancer 1 (DLC1) were associated with increased sensitivity to a ROCK inhibitor. Therefore, our study strongly suggests that BCL2L1 and DLC1 can serve as targets for novel GC therapies. Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Recent high-throughput analyses of genomic alterations revealed several driver genes and altered pathways in GC. However, therapeutic applications from genomic data are limited, largely as a result of the lack of druggable molecular targets and preclinical models for drug selection. To identify new therapeutic targets for GC, we performed array comparative genomic hybridization (aCGH) of DNA from 103 patients with GC for copy number alteration (CNA) analysis, and whole-exome sequencing from 55 GCs from the same patients for mutation profiling. Pathway analysis showed recurrent alterations in the Wnt signaling [APC, CTNNB1, and DLC1 (deleted in liver cancer 1)], ErbB signaling (ERBB2, PIK3CA, and KRAS), and p53 signaling/apoptosis [TP53 and BCL2L1 (BCL2-like 1)] pathways. In 18.4% of GC cases (19/103), amplification of the antiapoptotic gene BCL2L1 was observed, and subsequently a BCL2L1 inhibitor was shown to markedly decrease cell viability in BCL2L1-amplified cell lines and in similarly altered patient-derived GC xenografts, especially when combined with other chemotherapeutic agents. In 10.9% of cases (6/55), mutations in DLC1 were found and were also shown to confer a growth advantage for these cells via activation of Rho-ROCK signaling, rendering these cells more susceptible to a ROCK inhibitor. Taken together, our study implicates BCL2L1 and DLC1 as potential druggable targets for specific subsets of GC cases.
Plant Pathologist's Pocketbook.

The handbook for student and practising plant pathologists has been thoroughly reorganised and updated since the publication of the 2nd edition in 1983. Features include: rearrangement of topics to facilitate use; 49 short succinct chapters, each providing practical information; new topics - landmarks in plant pathology, survey of sampling procedures, disease evaluation, effects of climate change, biochemical and molecular techniques, epidemic modelling, breeding for resistance, laboratory safety and electronic databases; and seven overall section covering disease recognition and evaluation, causation, diagnosis, investigation, control, general techniques, and presentation of results.
The relationship between acute and chronic aerobic exercise response in pre-hypertensive individuals

Aerobic exercise is recommended as a lifestyle intervention to reduce blood pressure (BP) in individuals with elevated BP (SBP/DBP >120/80 mmHg). However, the BP response is highly variable after both acute (SBP/DBP: –27 to 9/-8 to 7mmHg) and chronic aerobic exercise (-20 to 9/ -11 to 11.3mmHg). We attempt to identify those who are resistant or responsive to training based on their responses to acute (one-bout) exercise. 17 prehypertensive (120 to 139/80 to 89mmHg) males and females (45-60yrs) underwent acute exercise assessments before and after an 8-week walking/jogging program. The magnitude of change in BP after acute exercise significantly correlated (r=.89, p < .01) with the magnitude of change in resting BP after the training. The antihypertensive mechanisms (total peripheral resistance, baroreflex sensitivity) for acute exercise were not correlated to those for chronic exercise. Central cardiovascular controls may link BP reductions after both acute and chronic exercise.
Transitions into and out of light and intermittent smoking during emerging adulthood.

INTRODUCTION The purpose of this study was to examine transitions in smoking from adolescence into emerging adulthood and to identify factors that might influence these transitions, specifically, movement into and out of light and intermittent smoking. METHODS This study used Markov models to examine movement across three stages of smoking (nonsmoking, light and intermittent smoking, and heavy smoking) from adolescence into emerging adulthood. Biannual data were collected from 990 young men and women from the 12th grade until 2 years after high school. RESULTS At each timepoint, most youth were nonsmokers. Those who were heavy smokers in 12th grade had a 79% chance of also being heavy smokers 2 years after high school. Between 17% and 21% of participants were light and intermittent smokers at each timepoint, and the likelihood of remaining so at the next timepoint ranged from 56% to 72%. Less than one-half of the 12th-grade light and intermittent smokers were light and intermittent smokers 2 years later, and 3% of the sample were light and intermittent smokers across all assessments. Prevalence and transition rates did not differ by gender. College attendees reported less smoking than nonattendees before and after their transition to college, and attendees compared with nonattendees who smoked were less likely to transition from light and intermittent to heavy smoking and remain heavy smokers. Binge drinking was significantly related to 12th-grade smoking stage and to transitions from nonsmoking to smoking. Overall, few emerging adults maintained light and intermittent smoking consistently over time. DISCUSSION Light and intermittent smoking during emerging adulthood may not be the same phenomenon as light and intermittent smoking in adulthood.
Estimating smokers' mouth-level exposure to select mainstream smoke constituents from discarded cigarette filter butts.

INTRODUCTION Standardized machine smoking measurements are poor predictors of exposure. We have refined a method using the solanesol deposited in discarded cigarette butts as a marker for estimating deliveries of mainstream smoke constituents. Developing a fast and accurate method for measuring solanesol in cigarette filters to assess tobacco smoke intake could provide a way to assess how people smoke under natural conditions. We have developed and validated a new, lower-cost, high-throughput method to measure the solanesol content in discarded cigarette filter butts and correlated these measurements with mainstream smoke deliveries of nicotine and tobacco-specific nitrosamines (TSNAs). METHODS Cigarettes were machine smoked under a variety of conditions to cover a wide range of nicotine deliveries and solanesol levels in the spent cigarette filter. Following machine smoking, a 1-cm portion of filter material, measured from the mouth end, was removed from the cigarette butts for analysis. Although an isotopically labeled solanesol analog is currently not commercially available, we achieved excellent quantitative results using a structurally similar compound, geranylgeraniol, as an internal standard (IS). After spiking with IS and solvent extracted, solanesol extracts were then analyzed using liquid chromatography coupled with a single-quadrupole mass analyzer. Analysis was carried out using manual preparation as well as a high-throughput 48-well format using automated liquid handlers. RESULTS Recoveries of solanesol from cigarette butts exceeded 95% with excellent precision and exhibited excellent linearity for both preparation methods. In addition, we show that the mouth-level exposure for both nicotine and TSNAs may be estimated by their relation to the solanesol retained in the cigarette filter. DISCUSSION We believe that this method provides excellent versatility and throughput for the estimation of mouth-level exposure to a wide range of toxins in cigarette smoke under naturalistic conditions. In addition, this method allows a far more accurate measure of exposure both from a single cigarette as well as from daily smoking.