Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct phytochrome actions in nonvascular plants revealed by targeted inactivation of phytobilin biosynthesis

The red/far-red light photoreceptor phytochrome mediates photomorphological responses in plants. For light sensing and signaling, phytochromes need to associate with open-chain tetrapyrrole molecules as the chromophore. Biosynthesis of tetrapyrrole chromophores requires members of ferredoxin-dependent bilin reductases (FDBRs). It was shown that LONG HYPOCOTYL 2 (HY2) is the only FDBR in flowering plants producing the phytochromobilin (PΦB) for phytochromes. However, in the moss Physcomitrella patens, we found a second FDBR that catalyzes the formation of phycourobilin (PUB), a tetrapyrrole pigment usually found as the protein-bound form in cyanobacteria and red algae. Thus, we named the enzyme PUB synthase (PUBS). Severe photomorphogenic phenotypes, including the defect of phytochrome-mediated phototropism, were observed in Physcomitrella patens when both HY2 and PUBS were disrupted by gene targeting. This indicates HY2 and PUBS function redundantly in phytochrome-mediated responses of nonvascular plants. Our studies also show that functional PUBS orthologs are found in selected lycopod and chlorophyte genomes. Using mRNA sequencing for transcriptome profiling, we demonstrate that expression of the majority of red-light-responsive genes are misregulated in the pubs hy2 double mutant. These studies showed that moss phytochromes rapidly repress expression of genes involved in cell wall organization, transcription, hormone responses, and protein phosphorylation but activate genes involved in photosynthesis and stress signaling during deetiolation. We propose that, in nonvascular plants, HY2 and PUBS produce structurally different but functionally similar chromophore precursors for phytochromes. Holophytochromes regulate biological processes through light signaling to efficiently reprogram gene expression for vegetative growth in the light.
Primary epimutations introduced during intracytoplasmic sperm injection (ICSI) are corrected by germline-specific epigenetic reprogramming

The use of assisted reproductive technologies (ART) has become increasingly common worldwide and is now responsible for 2–3% of children born in developed countries. Multiple reports have suggested that ART-conceived children are more likely to develop rare epigenetic disorders such as Beckwith-Wiedemann Syndrome or Angelman Syndrome, both of which involve dysregulation of imprinted genes. Anecdotal reports suggest that animals produced with ART that manifest apparent epigenetic defects typically do not transmit these epimutations to subsequent generations when allowed to breed naturally, but this hypothesis has not been directly studied. We analyzed allele-specific DNA methylation and expression at three imprinted genes, H19, Snrpn, and Peg3, in somatic cells from adult mice generated with the use of intracytoplasmic sperm injection (ICSI), a type of ART. Epimutations were detected in most of the ICSI-derived mice, but not in somatic cells of their offspring produced by natural mating. We examined germ cells from the ICSI mice that exhibited epimutations in their somatic cells and confirmed normal epigenetic reprogramming of the three imprinted genes analyzed. Collectively, these results confirm that ART procedures can lead to the formation of primary epimutations, but while such epimutations are likely to be maintained indefinitely in somatic cells of the ART-derived individuals, they are normally corrected in the germ line by epigenetic reprogramming and thus, not propagated to subsequent generations.
Putting the concept of biological embedding in historical perspective

This paper describes evidence that led to the concept of biological embedding and research approaches designed to elucidates its mechanisms. Biological embedding occurs when experience gets under the skin and alters human biological and developmental processes; when systematic differences in experience in different social environments in society lead to systematically different biological and developmental states; when these differences are stable and long term; and, finally, when they have the capacity to influence health, well-being, learning, or behavior over the life course. Biological embedding emerged from insights in population health on the unique characteristics of socioeconomic gradients: Ubiquity in poor and postscarcity societies alike; gradient seen regardless of whether socioeconomic status is measured by income, education, or occupation; cutting widely across health, well-being, learning, and behavior outcomes; replicating itself on new conditions entering society; and, often, showing that flatter gradients mean better overall societal outcomes. Most important, the gradient begins the life course as a gradient in developmental health, suggesting that the emergence of a multifaceted resilience/vulnerability early in life is the best place to look for evidence of biological embedding. To understand its character, the metaphor of the “archeology of biological embedding” has been used, wherein the surficial stratum of the “dig” is experience and behavior, the shallow stratum is organ system and cellular function, and the deep stratum is gene function. We are now ready to address the fundamental question of biological embedding: How do early childhood environments work together with genetic variation and epigenetic regulation to generate gradients in health and human development across the life course?
A Mechanically Robust and Highly Ion‐Conductive Polymer‐Blend Coating for High‐Power and Long‐Life Lithium‐Ion Battery Anodes

A mechanically robust and ion-conductive polymeric coating containing two polymers, polyethylene glycol tert-octylphenyl ether and poly(allyl amine), with four tailored functional groups is developed for graphite and graphite-Si composite anodes. The coating, acting as an artificial solid electrolyte interphase, leads to remarkable enhancement in capacity reversibility and cycling stability, as well as a high-rate performance of the studied anodes.
Battle of the sexes: Conflict over dosage-sensitive genes and the origin of X chromosome inactivation

Males have been short-changed in the X chromosome department: they only get one copy of the chromosome and the genes that it carries, whereas females get two. Differences in gene dose often translate into differences in protein levels, potentially putting males at a disadvantage compared with their sisters. Female placental and marsupial mammals inactivate one of their two X chromosomes, effectively silencing gene expression from the inactive X and seemingly putting themselves at the same disadvantage as their brothers. In PNAS, Pessia et al. (1) show that female X chromosome inactivation (XCI) is not in fact an act of solidarity by females but rather a result of the evolutionary tug of war over gene expression and sex chromosome dosage compensation that occurs between the sexes on the X chromosome.
Hierarchical Porous Plasmonic Metamaterials for Reproducible Ultrasensitive Surface‐Enhanced Raman Spectroscopy

Hierarchical porous plasmonic metamaterials consisting of periodic nanoholes with tunable diameter and uniformly distributed mesopores over the bulk are developed as a new class of 3D surface-enhanced Raman spectroscopy (SERS) substrates. This multiscale architecture not only facilitates efficient cascaded electromagnetic enhancement but also provides an enormous number of Raman-active binding sites, exhibiting excellent reproducibility and ultrasensitive detection of aromatic molecules down to 10(-13) M.
Bodywide skipping of exons 45–55 in dystrophic mdx52 mice by systemic antisense delivery

Duchenne muscular dystrophy (DMD), the commonest form of muscular dystrophy, is caused by lack of dystrophin. One of the most promising therapeutic approaches is antisense-mediated elimination of frame-disrupting mutations by exon skipping. However, this approach faces two major hurdles: limited applicability of each individual target exon and uncertain function and stability of each resulting truncated dystrophin. Skipping of exons 45–55 at the mutation hotspot of the DMD gene would address both issues. Theoretically it could rescue more than 60% of patients with deletion mutations. Moreover, spontaneous deletions of this specific region are associated with asymptomatic or exceptionally mild phenotypes. However, such multiple exon skipping of exons 45–55 has proved technically challenging. We have therefore designed antisense oligo (AO) morpholino mixtures to minimize self- or heteroduplex formation. These were tested as conjugates with cell-penetrating moieties (vivo-morpholinos). We have tested the feasibility of skipping exons 45–55 in H2K-mdx52 myotubes and in mdx52 mice, which lack exon 52. Encouragingly, with mixtures of 10 AOs, we demonstrated skipping of all 10 exons in vitro, in H2K-mdx52 myotubes and on intramuscular injection into mdx52 mice. Moreover, in mdx52 mice in vivo, systemic injections of 10 AOs induced extensive dystrophin expression at the subsarcolemma in skeletal muscles throughout the body, producing up to 15% of wild-type dystrophin protein levels, accompanied by improved muscle strength and histopathology without any detectable toxicity. This is a unique successful demonstration of effective rescue by exon 45–55 skipping in a dystrophin-deficient animal model.
Long‐term survivability of hydroxyapatite‐coated implants: a meta‐analysis

Objective: Numerous studies have showed a primary stability of dental implant coated with hydroxyapatite (HA). However, over the long-term stability of the HA-coated implant the discussion is still controversial. Present study focuses on literature analysis in order to evaluate the long-term clinic outcome of HA-coated implants. Materials and methods: Concerning the survival of HA-coated implants a systematic search for English literature over clinical trials (published from 1996 to 2009) was performed. On the basis of the inclusion criteria, nine studies were selected for final data analysis, which included 1051 patients with 3470 HA-coated dental implants. Clinical treatment followed a two stage surgical approach with an unloaded healing period of 3–6 months. The period of clinical follow-up ranged from 3 to 10 years. The obtained data were statistically analysed using chi-square test. Cumulative survival rate (CSR) and success rate were calculated. Results: The overall cumulative survival rate over 5 years was 93.15% compared with the success rate of 86.12%. The 10-year CSR was 87.39% compared with the 10-year success rate of 63.84%. There was significant difference between CSR and success rate (P 0.05). Conclusions: The 5-year CSR is better than the 10-year results, but without significant difference; the survival rates reported for HA-coated implants were similar to the other implants, but the success rates were significantly lower than the overall survival rates.
Degradation and resilience in Louisiana salt marshes after the BP–Deepwater Horizon oil spill

More than 2 y have passed since the BP–Deepwater Horizon oil spill in the Gulf of Mexico, yet we still have little understanding of its ecological impacts. Examining effects of this oil spill will generate much-needed insight into how shoreline habitats and the valuable ecological services they provide (e.g., shoreline protection) are affected by and recover from large-scale disturbance. Here we report on not only rapid salt-marsh recovery (high resilience) but also permanent marsh area loss after the BP–Deepwater Horizon oil spill. Field observations, experimental manipulations, and wave-propagation modeling reveal that (i) oil coverage was primarily concentrated on the seaward edge of marshes; (ii) there were thresholds of oil coverage that were associated with severity of salt-marsh damage, with heavy oiling leading to plant mortality; (iii) oil-driven plant death on the edges of these marshes more than doubled rates of shoreline erosion, further driving marsh platform loss that is likely to be permanent; and (iv) after 18 mo, marsh grasses have largely recovered into previously oiled, noneroded areas, and the elevated shoreline retreat rates observed at oiled sites have decreased to levels at reference marsh sites. This paper highlights that heavy oil coverage on the shorelines of Louisiana marshes, already experiencing elevated retreat because of intense human activities, induced a geomorphic feedback that amplified this erosion and thereby set limits to the recovery of otherwise resilient vegetation. It thus warns of the enhanced vulnerability of already degraded marshes to heavy oil coverage and provides a clear example of how multiple human-induced stressors can interact to hasten ecosystem decline.
Furin‐Mediated Sequential Delivery of Anticancer Cytokine and Small‐Molecule Drug Shuttled by Graphene

A cellular protease (furin)-mediated graphene-based nanosystem is developed for co-delivery of a membrane-associated cytokine (tumor-necrosis-factor-related apoptosis-inducing ligand, TRAIL) and an intracellular-acting small-molecule drug (Doxorubicin, DOX). TRAIL and DOX can be sequentially released toward the plasma membrane and nucleus, respectively.
High-frequency self-aligned graphene transistors with transferred gate stacks

Graphene has attracted enormous attention for radio-frequency transistor applications because of its exceptional high carrier mobility, high carrier saturation velocity, and large critical current density. Herein we report a new approach for the scalable fabrication of high-performance graphene transistors with transferred gate stacks. Specifically, arrays of gate stacks are first patterned on a sacrificial substrate, and then transferred onto arbitrary substrates with graphene on top. A self-aligned process, enabled by the unique structure of the transferred gate stacks, is then used to position precisely the source and drain electrodes with minimized access resistance or parasitic capacitance. This process has therefore enabled scalable fabrication of self-aligned graphene transistors with unprecedented performance including a record-high cutoff frequency up to 427 GHz. Our study defines a unique pathway to large-scale fabrication of high-performance graphene transistors, and holds significant potential for future application of graphene-based devices in ultra–high-frequency circuits.
A Multimaterial Bioink Method for 3D Printing Tunable, Cell‐Compatible Hydrogels

A multimaterial bio-ink method using polyethylene glycol crosslinking is presented for expanding the biomaterial palette required for 3D bioprinting of more mimetic and customizable tissue and organ constructs. Lightly crosslinked, soft hydrogels are produced from precursor solutions of various materials and 3D printed. Rheological and biological characterizations are presented, and the promise of this new bio-ink synthesis strategy is discussed.
Isolated retrograde amnesia: clinical description and neuroimages of a case

SUMMARY Isolated retrograde amnesia is an uncommon Neuropsychological deficit and its etiology, clinical features, imaging and recovery have been poorly documented. This article reports the clinical case of a 28 year old female patient, resident in Medellin, Colombia, who after a kidnapping, suffers loss of remote memory. The patient received neuropsychological assessment, structural and functional neuroimaging studies, in order to characterize a possible neurological damageKEY WORDS: Neuropsychology, Retrograde Amnesia, Retrograde Memory Loss, Isolated Retrograde Amnesia (MeSH). Recibido: 20/02/14. Aceptado: 03/07/14. Correspondencia: Julian Carvajal-Castrillon: julian.carvajalcastrillon@gmail.com(1) Psicologa. Especialista en Rehabilitacion Neuropsicologica, Clinica CES(2) Neurorradiologo(3) Ingeniero de sistemas e Informatica, Magister en ingenieria en el area de imagenes medicas(4) Psicologo. Especialista en Rehabilitacion Neuropsicologica. Instituto Neurologico de Colombia INTRODUCCION
Macroscopic Single‐Crystal Gold Microflakes and Their Devices

A facile, green procedure is proposed to synthesize single-crystal gold microflakes with planar area up to 10(4) mu m(2). This unprecedented dimension offers new possibilities in designing flexible conductive films with tunable strain-dependent conductivity, that can be exploited in strain/force/vibration sensing devices. By using top-down micro-/nanofabrication techniques, these materials may further find use in single-crystal electronics and plasmonic applications.
Towards improved cardiovascular management: the necessity of combining blood pressure and fluid overload.

BACKGROUND Hypertension and fluid overload (FO) are well-recognized problems in the chronic kidney disease (CKD) population. While the prevalence of hypertension is well documented, little is known about the severity of FO in this population. METHODS A new bioimpedance spectroscopy device (BCM-Body Composition Monitor) was selected that allows quantitative determination of the deviation in hydration status from normal ranges (DeltaHS). Pre-dialysis systolic blood pressure (BPsys) and DeltaHS was analysed in 500 haemodialysis patients from eight dialysis centres. A graphical tool (HRP-hydration reference plot) was devised allowing DeltaHS to be combined with measurements of BPsys enabling comparison with a matched healthy population (n = 1244). RESULTS Nineteen percent of patients (n = 95) were found to have normal BPsys and DeltaHS in the normal range. Approximately one-third of patients (n = 133) exhibited reasonable control of BPsys and fluids (BPsys <150 mmHg and DeltaHS <2.5 L). In only 15% of patients (n = 74) was hypertension observed (BPsys >150 mmHg) with a concomitant DeltaHS >2.5 L (possible volume-dependent hypertension). In contrast, 13% of patients (n = 69) were hypertensive with DeltaHS <1.1 L (possible essential hypertension). In 10% of patients (n = 52), BPsys <140 mmHg was recorded despite DeltaHS exceeding 2.5 L. CONCLUSION Our study illustrated the wide variability in BPsys regardless of the degree of DeltaHS. The HRP provides an invaluable tool for classifying patients in terms of BPsys and DeltaHS and the proximity of these parameters to reference ranges. This represents an important step towards more objective choice of strategies for the optimal treatment of hypertension and FO. Further studies are required to assess the prognostic and therapeutic role of the HRP.
Maximizing inhibition of the renin-angiotensin system with high doses of converting enzyme inhibitors or angiotensin receptor blockers.

Over the last 20 years, inhibitors of the renin–angiotensin– aldosterone system (RAAS) have become the cornerstone inthetreatmentofhypertension.Likewise,thesedrugshave found an increasing use in patients with underlying renal disease, as numerous lines of evidence have pointed to theirhavingabloodpressureloweringindependent antiproteinuric effect [1]. This effect of renin–angiotensin system (RAS)inhibitorsgainsinsignificanceasseverallargeinterventional studies have uniformly found that proteinuria is a major risk factor for progression of renal disease [2–5]. In fact, in some of these studies [3,4] the reduction of proteinuria in patients with diabetic nephropathy was associated with a decreased risk of reaching a renal endpoint which included doubling of serum creatinine and end-stage renal disease (ESRD). A similar observation has been made in non-diabetic kidney disease with lower levels of baseline proteinuria [5], demonstrating the importance of lowering protein excretion in a variety of renal disorders and across a broad spectrum of protein excretions. In view of the above-described observations, it is not surprising that there have been attempts to determine whether inhibition of the renin–angiotensin system at various levels could produce additive renoprotective effects. With the advent of a direct renin inhibitor (DRI), in addition to converting enzyme inhibitors (ACEs) and angiotensin receptor blockers (ARBs), there are no less than four potential drug combinations. Furthermore, since antagonists of aldosterone have been shown to decrease protein excretion in patients with renal diseases [6,7], the option of also employing aldosterone inhibitors doubles the potential combination of drugs to eight (Table 1). As would be expected, the most frequently used combination is that of an ACE with an ARB. Many of the studies that have been undertaken with this approach suffer from the confounding effect of further blood pressure lowering with the dual treatment, particularly when the doses used in the combination were the same as those employed in the comparator monotherapies [8]. However, when taken together, in a thoroughly and
Optimizing risk predictive strategies in febrile neutropenic episodes in children and young people undergoing treatment for malignant disease

The aim of this thesis was to investigate the clinical problem of the initial management of febrile neutropenia (FN) in children and young people undergoing treatment for malignant disease, to thoroughly evaluate the existing research, and to collect and synthesise this to quantify the risk of adverse clinical outcomes, through development of develop a new risk prediction model, using individual participant data (IPD). A further aim was to develop methodological approaches to IPD analysis in the development of predictive models, including the graphical display and communication of such information. The research produced five systematic reveiws of the existing medical literature in this area, and helped create a global collaboration of 19 research groups (PICNICC) which has shared data on over 5000 episodes of FN. This individual patient data was synthesised using hierarchical logistic regression meta-analysis to develop a new predictive model for MDI, which is robust to internal validation techniques (bootstrapping and leave-one-out cross-validation). The multivariable predictive model derived had six components: Tumour type, temperature, clinical description of being “severely unwell”, and the results of measurements of three elements of the full blood count: haemoglobin concentration, total white cell count and absolute monocyte count. It showed good overall fit (Brier[scaled] 4.5% discordancy), moderate discrimination (AU-ROC 0.736) and good calibration between predicted and actual estimates of the risk of MDI (calibration slope 0.95). We have demonstrated that such a data sharing project is feasible across many different jurisdictions and eras of study, and we now need to undertake a series of further projects to evaluate the model and go on to improve the management of paediatric FN across the world.