Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective benefits of damage partitioning in unicellular systems and its effects on aging

Cytokinesis in unicellular organisms sometimes entails a division of labor between cells leading to lineage-specific aging. To investigate the potential benefits of asymmetrical cytokinesis, we created a mathematical model to simulate the robustness and fitness of dividing systems displaying different degrees of damage segregation and size asymmetries. The model suggests that systems dividing asymmetrically (size-wise) or displaying damage segregation can withstand higher degrees of damage before entering clonal senescence. When considering population fitness, a system producing different-sized progeny like budding yeast is predicted to benefit from damage retention only at high damage propagation rates. In contrast, the fitness of a system of equal-sized progeny is enhanced by damage segregation regardless of damage propagation rates, suggesting that damage partitioning may also provide an evolutionary advantage in systems dividing by binary fission. Indeed, by using Schizosaccharomyces pombe as a model, we experimentally demonstrate that damaged proteins are unevenly partitioned during cytokinesis and the damage-enriched sibling suffers from a prolonged generation time and accelerated aging. This damage retention in S. pombe is, like in Saccharomyces cerevisiae, Sir2p- and cytoskeleton-dependent, suggesting this to be an evolutionarily conserved mechanism. We suggest that sibling-specific aging may be a result of the strong selective advantage of damage segregation, which may be more common in nature than previously anticipated.
Benzodiazepines revisited--will we ever learn?

AIMS To re-examine various aspects of the benzodiazepines (BZDs), widely prescribed for 50 years, mainly to treat anxiety and insomnia. It is a descriptive review based on the Okey Lecture delivered at the Institute of Psychiatry, King's College London, in November 2010. METHODS A search of the literature was carried out in the Medline, Embase and Cochrane Collaboration databases, using the codeword 'benzodiazepine(s)', alone and in conjunction with various terms such as 'dependence', 'abuse', etc. Further hand-searches were made based on the reference lists of key papers. As 60,000 references were found, this review is not exhaustive. It concentrates on the adverse effects, dependence and abuse. RESULTS Almost from their introduction the BZDs have been controversial, with polarized opinions, advocates pointing out their efficacy, tolerability and patient acceptability, opponents deprecating their adverse effects, dependence and abuse liability. More recently, the advent of alternative and usually safer medications has opened up the debate. The review noted a series of adverse effects that continued to cause concern, such as cognitive and psychomotor impairment. In addition, dependence and abuse remain as serious problems. Despite warnings and guidelines, usage of these drugs remains at a high level. The limitations in their use both as choice of therapy and with respect to conservative dosage and duration of use are highlighted. The distinction between low-dose 'iatrogenic' dependence and high-dose abuse/misuse is emphasized. CONCLUSIONS The practical problems with the benzodiazepines have persisted for 50 years, but have been ignored by many practitioners and almost all official bodies. The risk-benefit ratio of the benzodiazepines remains positive in most patients in the short term (2-4 weeks) but is unestablished beyond that time, due mainly to the difficulty in preventing short-term use from extending indefinitely with the risk of dependence. Other research issues include the possibility of long-term brain changes and evaluating the role of the benzodiazepine antagonist, flumazenil, in aiding withdrawal.
Army nurse officer retention : a qualitative examination of forces influencing the career longevity of army nurses

"Having fewer nursing personnel to treat patients contributes to increased patient morbidity and mortality and decreased quality care. The U.S. Army faces challenges in its nurse recruitment. Thus, retention of qualified nursing staff is imperative for the Army Nurse Corps (ANC) to provide nursing care to soldiers, retirees, and families worldwide. A stratified, purposive, non-probability sample of 6 officers was interviewed to identify and describe forces affecting retention. Influential forces are numerous and complex. The factors contributing to ANC officer retention were segregated into two global categories: personal desire and emotional investment. Personal desire included intent, career investment, need fulfillment, and benefits, while emotional investment consisted of satisfaction, challenge, and comfort. The life events contributing to ANC officer retention were also segregated into two global categories: organizational environment and personal situation. Organizational environment included education, leadership, and work environment, while personal situation consisted of familial factors, need fulfillment, and comfort. The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. "--Abstract from author supplied metadata.
Integrin α2β1 plays a critical role in osteoblast response to micron-scale surface structure and surface energy of titanium substrates

Efforts to improve bone response to biomaterials have focused on ligands that bind α5β1 integrins. However, antibodies to α5β1 reduce osteoblast proliferation but do not affect differentiation when cells are grown on titanium (Ti). β1-silencing blocks the differentiation stimulus of Ti microtopography, suggesting that other β1 partners are important. Stably α2-silenced MG63 human osteoblast-like cells were used to test whether α2β1 specifically mediates osteoblast response to Ti surface micron-scale structure and energy. WT and α2-silenced MG63 cells were cultured on tissue culture polystyrene (TCPS) and Ti disks with different surface microtopographies: machined pretreatment (PT) surfaces [mean peak to valley roughness (Ra) < 0.02 μm], PT surfaces that were grit-blasted and acid-etched (SLA; Ra = 4 μm), and SLA with high surface energy (modSLA). Alkaline phosphatase (ALP), α2 and β1 mRNA, but not α5, αv, β3, type-I collagen, or osteocalcin, increased on SLA and modSLA at 6 days. α2 increased at 8 days on TCPS and PT, but remained unchanged on SLA and modSLA. α2-protein was reduced 70% in α2-siRNA cells, whereas α5-mRNA and protein were unaffected. α2-knockdown blocked surface-dependent increases in β1 and osteocalcin and decreases in cell number and increases in ALP and local factors typical of MG63 cells grown on SLA and modSLA [e.g., prostaglandin E2, osteoprotegerin, latent and active TGF-β1, and stimulatory effects of 1α,25(OH)2D3 on these parameters]. This finding indicates that α2β1 signaling is required for osteoblastic differentiation caused by Ti microstructure and surface energy, suggesting that conclusions based on cell behavior on TCPS are not predictive of behavior on other substrates or the mechanisms involved.
B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver

Dysregulated Wnt signaling is seen in approximately 30% of hepatocellular carcinomas; thus, finding pathways downstream of the activation of Wnt signaling is key. Here, using cre-lox technology, we deleted the Apc gene in the adult mouse liver and observed a rapid increase in nuclear β-catenin and c-Myc, which is associated with an induction of proliferation that led to hepatomegaly within 4 days of gene deletion. To investigate the downstream pathways responsible for these phenotypes, we analyzed the impact of inactivating APC in the context of deficiency of the potentially key effectors β-catenin and c-Myc. β-catenin loss rescues both the proliferation and hepatomegaly phenotypes after APC loss. However, c-Myc deletion, which rescues the phenotypes of APC loss in the intestine, had no effect on the phenotypes of APC loss in the liver. The consequences of the deregulation of the Wnt pathway within the liver are therefore strikingly different from those observed within the intestine, with the vast majority of Wnt targets being β-catenin-dependent but c-Myc-independent in the liver.
From the shards of a shattered genome, diversity

Ionizing radiation (IR) poses a severe threat to genome stability, inducing base changes, cross-links, and double-stranded breaks (DSBs). Improper repair of IR damage has severe consequences, frequently resulting in formation of chromosomal translocations leading to gene dysregulation at translocation breakpoints and/or oncogenic fusions. Moreover, cancer genomes are very severely rearranged. Thus, there is great interest in determining the origins of spontaneous genome rearrangement. Homologous recombination (HR) has long been implicated in the recovery from irradiation, as evidenced by the sensitivity of rad52 yeast strains to irradiation (1, 2). In this issue of PNAS, Argueso et al. (3) demonstrate not only that HR is the primary mechanism by which DSBs are repaired in diploid yeast cells recovering from IR, but also that chromosomal aberrations (CAs) are generated by recombination between nonallelic repeats and that this process profoundly reshapes the genome of surviving cells.
COLLABORATIVE PRACTICES IN MENTAL HEALTH CARE: MULTIDISCIPLINARY TEAMWORK OR INTER-PROFESSIONAL COLLABORATION GROUPS?

BACKGROUND: Multidisciplinary teams (MDT) have proven their effectiveness in health care services, especially when they meet the criteria for teams as well and are not multidisciplinary groups of professionals or pseudo-teams. METHODS: An electronic questionnaire has been designed and distributed to members of 18 Romanian Community Mental Health Centers (CMHC) in order to diagnose the collaborative practices as well as the most frequent types of inter-professional contact used in Romanian CMHCs. RESULTS: Although 95% of the professionals investigated report that they work in “a team”, team meetings are not organized or are organized at time intervals higher than a month in 67,5% of cases. CONCLUSION: The development of teamwork booster sessions for CMHC members as well as the implementation of financial and non-financial incentives for teamwork could contribute to increased coordination and efficacy of mental health services. Keywords: multidisciplinary teams (MDT), Community Mental Health Center (CMHC)
The Use of Uterine Artery Embolisation in the Management of Fibroids. Clinical Recommendations

Arterial embolisation has been used as a method of treating haemorrhage in a variety of clinical situations, including postpartum haemorrhage, bleeding after caesarean section and bleeding following gynaecological surgery. These recommendations aims to provide guidelines for clinicians involved in care of patients undergoing uterine artery embolisation (UAE) for fibroids. Summary of recommendations: 1. The early and mid-term results of UAE are promising indicating that it is as least as safe as the surgical alternatives. It provides good symptom relief and is particularly effective for heavy menstrual bleeding. 2. For women with symptomatic fibroids, UAE should be considered as one of the treatment options as well as the conventional surgical treatments such as myomectomy and hysterectomy. 3. UAE as treatment for fibroids in women of child-bearing age who wish, or might wish, to become pregnant in the future should only be offered after fully informed discussion and should be considered on a case-by-case basis. The increased risks of caesarean section and the possibility of increased pregnancy complications should be fully understood. 4. The procedure is contraindicated in women who have evidence of current or recent infection, women who are unwilling to have a hysterectomy in any circumstances and where there is significant doubt about the diagnosis of benign pathology. 5. Patients should be seen by a gynaecologist and accurate pretreatment diagnosis is essential. MRI is recommended but good quality ultrasound is the minimum imaging requirement. 6. The procedure should only be undertaken by radiologists with specialised experience in embolisation who have undergone appropriate training. 7. The particular responsibilities of both gynaecologist and radiologist should be established prior to treatment and be set out in a relevant hospital protocol. The patient must be under a named responsible consultant at all times. Careful follow-up protocols should be established. 8. These recommendations are intended for both the National Health Service and the private sector. Article in Lithuanian doi:10.5200/sm-hs.2012. 081
Molecular structural basis for polymorphism in Alzheimer's β-amyloid fibrils

We describe a full structural model for amyloid fibrils formed by the 40-residue β-amyloid peptide associated with Alzheimer's disease (Aβ1–40), based on numerous constraints from solid state NMR and electron microscopy. This model applies specifically to fibrils with a periodically twisted morphology, with twist period equal to 120 ± 20 nm (defined as the distance between apparent minima in fibril width in negatively stained transmission electron microscope images). The structure has threefold symmetry about the fibril growth axis, implied by mass-per-length data and the observation of a single set of 13C NMR signals. Comparison with a previously reported model for Aβ1–40 fibrils with a qualitatively different, striated ribbon morphology reveals the molecular basis for polymorphism. At the molecular level, the 2 Aβ1–40 fibril morphologies differ in overall symmetry (twofold vs. threefold), the conformation of non-β-strand segments, and certain quaternary contacts. Both morphologies contain in-register parallel β-sheets, constructed from nearly the same β-strand segments. Because twisted and striated ribbon morphologies are also observed for amyloid fibrils formed by other polypeptides, such as the amylin peptide associated with type 2 diabetes, these structural variations may have general implications.
Compensatory IKKα activation of classical NF-κB signaling during IKKβ inhibition identified by an RNA interference sensitization screen

A subtype of diffuse large B-cell lymphoma (DLBCL), termed activated B-cell-like (ABC) DLBCL, depends on constitutive nuclear factor-κB (NF-κB) signaling for survival. Small molecule inhibitors of IκB kinase β (IKKβ), a key regulator of the NF-κB pathway, kill ABC DLBCL cells and hold promise for the treatment of this lymphoma type. We conducted an RNA interference genetic screen to investigate potential mechanisms of resistance of ABC DLBCL cells to IKKβ inhibitors. We screened a library of small hairpin RNAs (shRNAs) targeting 500 protein kinases for shRNAs that would increase the killing of an ABC DLBCL cell line in the presence of a small molecule IKKβ inhibitor. Two independent shRNAs targeting IKKα synergized with the IKKβ inhibitor to kill three different ABC DLBCL cell lines but were not toxic by themselves. Surprisingly, IKKα shRNAs blocked the classical rather than the alternative NF-κB pathway in ABC DLBCL cells, as judged by inhibition of IκBα phosphorylation. IKKα shRNA toxicity was reversed by coexpression of wild-type but not kinase inactive forms of IKKα, suggesting that IKKα may directly phosphorylate IκBα under conditions of IKKβ inhibition. In models of physiologic NF-κB pathway activation by CARD11 or tumor necrosis factor-α, compensatory IKKα activity was also observed with IKKβ inhibition. These results suggest that therapy for ABC DLBCL may be improved by targeting both IKKα and IKKβ, possibly through CARD11 inhibition.
Transformation mechanism of amorphous calcium carbonate into calcite in the sea urchin larval spicule

Sea urchin larval spicules transform amorphous calcium carbonate (ACC) into calcite single crystals. The mechanism of transformation is enigmatic: the transforming spicule displays both amorphous and crystalline properties, with no defined crystallization front. Here, we use X-ray photoelectron emission spectromicroscopy with probing size of 40–200 nm. We resolve 3 distinct mineral phases: An initial short-lived, presumably hydrated ACC phase, followed by an intermediate transient form of ACC, and finally the biogenic crystalline calcite phase. The amorphous and crystalline phases are juxtaposed, often appearing in adjacent sites at a scale of tens of nanometers. We propose that the amorphous-crystal transformation propagates in a tortuous path through preexisting 40- to 100-nm amorphous units, via a secondary nucleation mechanism.
Achieving international progress on alcohol and traffic safety.

dents in these countries. Much is expected from this emerging research tradition, but there is already good evidence from studies in developed societies which show that high rates (up to 40% in New Zealand) of crash injuries are suffered by people who were not drinking [8]. That a significantly high proportion of the health and economic burden associated with drunk-driving accidents is borne by innocent passengers or pedestrians should be a sober reminder to policy makers in developing countries that the victim of drunk driving can be anyone. In subSaharan Africa the fundamental policy challenge is recognizing that a problem exists, and that the problem is amenable to effective interventions. There is reason for optimism: the global and regional strategies to reduce harmful use of alcohol developed by the World Health Organization (WHO) have led at least to serious discussions of policy strategies in many African countries, and the involvement of international nongovernmental organizations in training on evidencebased policy has helped to focus the attention of experts and policymakers on what works [9]. The gap between countries in how they respond to drinking and driving problems will remain for a long time but any country, whether in Africa or South America, can benefit from available knowledge on policy effectiveness as long as the realities of their particular contexts are always kept in view.
Mediator-assisted water oxidation by the ruthenium “blue dimer” cis,cis-[(bpy)2(H2O)RuORu(OH2)(bpy)2]4+

Light-driven water oxidation occurs in oxygenic photosynthesis in photosystem II and provides redox equivalents directed to photosystem I, in which carbon dioxide is reduced. Water oxidation is also essential in artificial photosynthesis and solar fuel-forming reactions, such as water splitting into hydrogen and oxygen (2 H2O + 4 hν → O2 + 2 H2) or water reduction of CO2 to methanol (2 H2O + CO2 + 6 hν → CH3OH + 3/2 O2), or hydrocarbons, which could provide clean, renewable energy. The “blue ruthenium dimer,” cis,cis-[(bpy)2(H2O)RuIIIORuIII(OH2)(bpy)2]4+, was the first well characterized molecule to catalyze water oxidation. On the basis of recent insight into the mechanism, we have devised a strategy for enhancing catalytic rates by using kinetically facile electron-transfer mediators. Rate enhancements by factors of up to ≈30 have been obtained, and preliminary electrochemical experiments have demonstrated that mediator-assisted electrocatalytic water oxidation is also attainable.
Indigo ‐ A Natural Pigment for High Performance Ambipolar Organic Field Effect Transistors and Circuits

Millenniums-old natural dye indigo--a "new" ambipolar organic semiconductor. Indigo shows balanced electron and hole mobilities of 1 × 10(-2) cm(2) V(-1) s(-1) and good stability against degradation in air. Inverters with gains of 105 in the first and 110 in the third quadrant are demonstrated. Fabricated entirely from natural and biodegradable compounds, these devices show the large potential of such materials for green organic electronics.
Differential degradation of PIN2 auxin efflux carrier by retromer-dependent vacuolar targeting

All eukaryotic cells present at the cell surface a specific set of plasma membrane proteins that modulate responses to internal and external cues and whose activity is also regulated by protein degradation. We characterized the lytic vacuole-dependent degradation of membrane proteins in Arabidopsis thaliana by means of in vivo visualization of vacuolar targeting combined with quantitative protein analysis. We show that the vacuolar targeting pathway is used by multiple cargos including PIN-FORMED (PIN) efflux carriers for the phytohormone auxin. In vivo visualization of PIN2 vacuolar targeting revealed its differential degradation in response to environmental signals, such as gravity. In contrast to polar PIN delivery to the basal plasma membrane, which depends on the vesicle trafficking regulator ARF-GEF GNOM, PIN sorting to the lytic vacuolar pathway requires additional brefeldin A-sensitive ARF-GEF activity. Furthermore, we identified putative retromer components SORTING NEXIN1 (SNX1) and VACUOLAR PROTEIN SORTING29 (VPS29) as important factors in this pathway and propose that the retromer complex acts to retrieve PIN proteins from a late/pre-vacuolar compartment back to the recycling pathways. Our data suggest that ARF GEF- and retromer-dependent processes regulate PIN sorting to the vacuole in an antagonistic manner and illustrate instrumentalization of this mechanism for fine-tuning the auxin fluxes during gravitropic response.
Sinergismo in vitro entre hidrazonas, ajoeno y posaconazol sobre aislados de Cryptococcus spp

El objetivo de este trabajo fue estudiar la susceptibilidad in vitro de aislados de Cryptocococus spp con una nueva clase de antifungicos, hidrazonas esteroidales y comparar su actividad antifungica en combinacion con ajoeno y posaconazol contra aislados de Cryptococcus spp. Se utilizaron tres aislados del genero Cryptococcus 42794, 4050 y 44192 y se evaluaron su sensibilidad y efectos sinergicos con las hidrazonas esteroidales, ajoeno y posaconazol, segun el documento M27-A2 del CLSI. Se incluyeron las cepas Candida albicans (ATCC 90028) y Candida parapsilosis (ATCC 22019) como controles. Se observo con las hidrazonas (H1, H2, H3, H4) un efecto plateau a partir de 10 μM (CMI). Sin embargo, con la H4 se obtuvo bajo porcentaje de inhibicion del crecimiento. Con el ajoeno, se obtuvieron valores de CMI de 25 y 50 μM. El posaconazol mostro altos valores de inhibicion y un valor de CMI de 6 μM para 42794 y 44192 y un CMI de 20 μM para el aislado 4050. Se obtuvieron efectos sinergicos al combinar posaconazol con ajoeno, ajoeno con hidrazona 3 y posaconazol con hidrazona 3. Los valores de concentracion inhibitoria fraccional fueron de 0,24; 0,16 y 0,09 respectivamente, indicando un marcado efecto sinergico. Se obtuvieron efectos sinergicos importantes entre el posaconazol con ajoeno, ajoeno con hidrazona 3 y posaconazol con hidrazona 3, lo cual seria muy util para futuros estudios clinicos.
Spatially Resolved Photodetection in Leaky Ferroelectric BiFeO3

Potential gradients due to the spontaneous polarization of BiFeO(3) yield asymmetric and nonlinear photocarrier dynamics. Photocurrent direction is determined by local ferroelectric domain orientation, whereas magnitude is spectrally centered around charged domain walls that are associated with oxygen vacancy migration. Photodetection can be electrically controlled by manipulating ferroelectric domain configurations.