Miracle-dz/UniFAR-FTUs huggingface dataset:
A rice high-affinity potassium transporter (HKT) conceals a calcium-permeable cation channel

Plant high-affinity K+ transport (HKT) proteins are so named because of their relation to bacterial and fungal transporters that mediate high-affinity K+ uptake. The view that HKT family members are sodium-selective uniporters or sodium-potassium symporters is widely held. We have found that one of the rice HKT proteins also functions as a Ca2+-permeable cation channel that conducts current carried by a wide range of monovalent and divalent cations. The HKT rice gene, named OsHKT2;4, is expressed in several cell types, including root hairs and vascular parenchyma cells. The protein is localized to the plasma membrane, thereby providing a mechanism for cation uptake and extrusion. This finding goes against firmly entrenched dogma in showing that HKT proteins can function as both ion carriers and channels. The study further extends the function of HKT proteins to Ca2+-linked processes and, in so doing, defines a previously undescribed type of Ca2+-permeable cation channels in plants. The work also raises questions about the evolutionary changes in this protein family following the divergence of monocots and dicots.
Rif1 promotes a repressive chromatin state to safeguard against endogenous retrovirus activation

Abstract Transposable elements, including endogenous retroviruses (ERVs), constitute a large fraction of the mammalian genome. They are transcriptionally silenced during early development to protect genome integrity and aberrant transcription. However, the mechanisms that control their repression are not fully understood. To systematically study ERV repression, we carried out an RNAi screen in mouse embryonic stem cells (ESCs) and identified a list of novel regulators. Among them, Rif1 displays the strongest effect. Rif1 depletion by RNAi or gene deletion led to increased transcription and increased chromatin accessibility at ERV regions and their neighboring genes. This transcriptional de-repression becomes more severe when DNA methylation is lost. On the mechanistic level, Rif1 directly occupies ERVs and is required for repressive histone mark H3K9me3 and H3K27me3 assembly and DNA methylation. It interacts with histone methyltransferases and facilitates their recruitment to ERV regions. Importantly, Rif1 represses ERVs in human ESCs as well, and the evolutionally-conserved HEAT-like domain is essential for its function. Finally, Rif1 acts as a barrier during somatic cell reprogramming, and its depletion significantly enhances reprogramming efficiency. Together, our study uncovered many previously uncharacterized repressors of ERVs, and defined an essential role of Rif1 in the epigenetic defense against ERV activation.
Reconstructing human evolution: Achievements, challenges, and opportunities

This contribution reviews the evidence that has resolved the branching structure of the higher primate part of the tree of life and the substantial body of fossil evidence for human evolution. It considers some of the problems faced by those who try to interpret the taxonomy and systematics of the human fossil record. How do you to tell an early human taxon from one in a closely related clade? How do you determine the number of taxa represented in the human clade? How can homoplasy be recognized and factored into attempts to recover phylogeny?
Intermolecular associations determine the dynamics of the circadian KaiABC oscillator

Three proteins from cyanobacteria (KaiA, KaiB, and KaiC) can reconstitute circadian oscillations in vitro. At least three molecular properties oscillate during this reaction, namely rhythmic phosphorylation of KaiC, ATP hydrolytic activity of KaiC, and assembly/disassembly of intermolecular complexes among KaiA, KaiB, and KaiC. We found that the intermolecular associations determine key dynamic properties of this in vitro oscillator. For example, mutations within KaiB that alter the rates of binding of KaiB to KaiC also predictably modulate the period of the oscillator. Moreover, we show that KaiA can bind stably to complexes of KaiB and hyperphosphorylated KaiC. Modeling simulations indicate that the function of this binding of KaiA to the KaiB•KaiC complex is to inactivate KaiA's activity, thereby promoting the dephosphorylation phase of the reaction. Therefore, we report here dynamics of interaction of KaiA and KaiB with KaiC that determine the period and amplitude of this in vitro oscillator.
Cytomegalovirus Infection in Liver Transplantation

With the global evolution of organ transplantation in humans a new class of patients with special problems related to opportunistic infections after transplantation has appeared [1, 2 ]. Some of these challenges infections with members of the herpesvirus family. Among these viruses, human cytomegalovirus (HCMV) often affects immunocompromised patients, HCMV can be reactivated by immunosuppression and cause significant morbidity and mortality [3,4]. In the postoperative period, HCMV infection can result in serious complica‐ tions in patients who received grafts by modulating the immune response [5]. However in immunocompetent individuals cytomegalovirus infection can be asymptomatic or cause symptoms similar to infectious mononucleosis syndrome, such as lymphadenopathy, fever, rash, malaise, arthralgia, hepatomegaly and splenomegaly [6].
Epidemiology and treatment effects in Chronic Obstructive Pulmonary Disease

textabstractChronic obstructive pulmonary disease (COPD) is a major health epidemic, which has important consequences for patients and community, and still receives insufficient attention from the health care professionals and scientists. COPD is a leading cause of chronic morbidity (affects 210 million people) and mortality (causes 3 million deaths per year) worldwide, and according to the World Health Organization (WHO), it is the fifth most common cause of death and the 10th most burdensome disease. The first definition of chronic obstructive pulmonary disease (COPD) can be found in the 60’s and incorporates both terms “emphysema” and “chronic bronchitis”. According to the Global Initiative for obstructive lung diseases (GOLD), COPD is defined as a “preventable and treatable disease with some significant extra-pulmonary effects that may contribute to the severity in individual patients. The pulmonary component is characterized by airflow limitation, which is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases, such as cigarette smoke”. COPD is clinically characterized by symptoms like cough, sputum production, and/or dyspnea. The diagnosis is confirmed by spirometry and accordingly has four stages, from mild (GOLD stage I) to very severe (GOLD stage IV). Patients with COPD typically have a decrease in both FEV1 and a FEV1/FVC ratio of less than 0.7. Using this ratio as cut-off point for all patients is currently questioned as it may underestimate COPD in the young and overestimate COPD in older populations. The GOLD definition has become globally accepted for the diagnosis of COPD and some crucial components of this definition have been incorporated by the European Respiratory Society (ERS) and by the American Thoracic Society (ATS).
Multifunctional, Ultra‐Flyweight, Synergistically Assembled Carbon Aerogels

All carbon aerogels (up to 1000 cm(3)) with ultralow density (down to 0.16 mg cm(-3)) and temperature-invariant (-190-900 °C) super-elasticity are fabricated by facile assembling of commercial carbon nanotubes (CNTs) and chemically-converted giant graphene sheets, on the basis of the synergistic effect between elastic CNTs ribs and giant graphene cell walls.
β1-integrin is dispensable for the induction of ErbB2 mammary tumors but plays a critical role in the metastatic phase of tumor progression

Cross-talk between integrin receptors and activated growth factor receptors has been hypothesized to play a critical role in the initiation and progression of cancer. Despite in vitro evidence documenting the important role of integrin receptors in the regulation of cancer cell proliferation, the relative contribution of the integrin receptors to the initiation and progression of tumors remains unclear. Previous studies with a polyomavirus middle T mammary tumor model have indicated that targeted disruption of β1-integrin in the mammary glands of these mice completely blocks tumor induction. To further explore the general significance of these observations, we have crossed these conditional β1-integrin strains to a strain of mice carrying mouse mammary tumor virus/activated erbB2 (herein referred to as the NIC strain). In contrast to the tumor induction block in the polyomavirus middle T model, tumor onset in the β1-integrin–deficient NIC mice was delayed by only 30 d and was 100% penetrant. This modest effect on tumor induction was not a result of inefficient excision, as all tumors were confirmed as β1-integrin–null. Animals bearing β1-integrin–deficient ErbB2 tumors exhibited significantly reduced tumor volume, which was associated with increased tumor cell apoptosis and a reduction in tumor angiogenesis. In addition, β1-integrin–deficient tumors were compromised in their capacity to metastasize to the lung, a deficiency associated with abrogation of adhesion signaling. Taken together, these observations suggest that, although β1-integrin is dispensable for the initiation of ErbB2 tumor induction, it plays a critical role in metastatic phase of tumor progression.
IL-33 is a crucial amplifier of innate rather than acquired immunity

IL-33, a member of the IL-1-related cytokines, is considered to be a proallergic cytokine that is especially involved in Th2-type immune responses. Moreover, like IL-1α, IL-33 has been suggested to act as an “alarmin” that amplifies immune responses during tissue injury. In contrast to IL-1, however, the precise roles of IL-33 in those settings are poorly understood. Using IL-1- and IL-33-deficient mice, we found that IL-1, but not IL-33, played a substantial role in induction of T cell-mediated type IV hypersensitivity such as contact and delayed-type hypersensitivity and autoimmune diseases such as experimental autoimmune encephalomyelitis. Most notably, however, IL-33 was important for innate-type mucosal immunity in the lungs and gut. That is, IL-33 was essential for manifestation of T cell-independent protease allergen-induced airway inflammation as well as OVA-induced allergic topical airway inflammation, without affecting acquisition of antigen-specific memory T cells. IL-33 was significantly involved in the development of dextran-induced colitis accompanied by T cell-independent epithelial cell damage, but not in streptozocin-induced diabetes or Con A-induced hepatitis characterized by T cell-mediated apoptotic tissue destruction. In addition, IL-33-deficient mice showed a substantially diminished LPS-induced systemic inflammatory response. These observations indicate that IL-33 is a crucial amplifier of mucosal and systemic innate, rather than acquired, immune responses.
Open vs specific questioning during anaesthetic follow‐up after Caesarean section

Words with negative emotional content such as pain or itch may enhance perception of these symptoms. We assessed open and direct questioning for symptoms in 100 women following Caesarean section. Of the 65 women reporting pain, 25 (39%) did so only when questioned specifically. Similarly, three women with bothersome pain (5%), and two requesting analgesia (3%), failed to disclose pain until questioned specifically. None of the 46 women with pain scores < 6 on a verbal numerical rating scale requested additional analgesia. Of 31 women with pruritus, two (6%) stated it bothered them and requested treatment and one (3%) failed to disclose pruritus on open questioning. Most women with bothersome pain or who request analgesia reveal this with open questioning. However, specific questioning is required to elicit pain in all patients. Most patients are bothered by pain at pain scores ≥ 6, while those with scores < 6 are unlikely to request additional analgesia.
Pediatric cancer patients’ peer relationships: The impact of an oncology camp experience

Increasing numbers of pediatric cancer patients attend summer camp sessions designed for them. Since 1976, more than 60 camps have been established in the United States alone. A major outcome of these experiences is the patients' formation of relationships that last beyond the camp sessions. Although these relationships are of major importance to the children, they do not replace their relationships with healthy peers. Each type of relationship fulfills different functions; the children value both. This article examines the children's perceptions of the advantages and disadvantages of both types of relationships.
Molecular basis for SH3 domain regulation of F-BAR–mediated membrane deformation

Members of the Bin/amphiphysin/Rvs (BAR) domain protein superfamily are involved in membrane remodeling in various cellular pathways ranging from endocytic vesicle and T-tubule formation to cell migration and neuromorphogenesis. Membrane curvature induction and stabilization are encoded within the BAR or Fer-CIP4 homology-BAR (F-BAR) domains, α-helical coiled coils that dimerize into membrane-binding modules. BAR/F-BAR domain proteins often contain an SH3 domain, which recruits binding partners such as the oligomeric membrane-fissioning GTPase dynamin. How precisely BAR/F-BAR domain-mediated membrane deformation is regulated at the cellular level is unknown. Here we present the crystal structures of full-length syndapin 1 and its F-BAR domain. Our data show that syndapin 1 F-BAR-mediated membrane deformation is subject to autoinhibition by its SH3 domain. Release from the clamped conformation is driven by association of syndapin 1 SH3 with the proline-rich domain of dynamin 1, thereby unlocking its potent membrane-bending activity. We hypothesize that this mechanism might be commonly used to regulate BAR/F-BAR domain-induced membrane deformation and to potentially couple this process to dynamin-mediated fission. Our data thus suggest a structure-based model for SH3-mediated regulation of BAR/F-BAR domain function.
Effect of nasal cannula oxygen administration on oxygen concentration at facial and adjacent landmarks

An oxygen‐enriched atmosphere enhances the potential for operating‐room fires. We thus determined oxygen concentrations at various facial landmarks during oxygen administration via nasal cannulae. Thirteen supine volunteers were draped similarly to patients undergoing a cervical‐node biopsy. Oxygen was delivered in random order through nasal cannulae at rates of 2, 4, and 6 l.min−1. Oxygen concentration was measured at pre‐determined facial landmarks and also distal to the drape at non‐facial sites. At a flow of 2 l.min−1, oxygen concentrations exceeded 23% only within a few centimetres of the nasal cannula. Concentration increased as a function of flow, but rarely exceeded 26%. At all flow rates, concentrations distal to the drape were < 24%. To reduce combustion risk, ignition sources should be kept at least 10 cm from the oxygen outlet when using nasal cannula at a flow rate ≥ 4 l.min−1.
Rectal Cancer Epidemiology

Colorectal cancer is the fourth most common cancer in men and the third most common one in women worldwide (Parkin, 2004; Parkin et al., 2005), accounting for approximately 436,000 incident cases and 212,000 deaths in 2008 (Quirke et al., 2011). This cancer has an important economic impact, estimating that in the initial, continuing and last year of life phases of care a total of more than $7 billion were spent (Yabroff et al., 2008). Randomized trials have shown that systematic screening of a target population of suitable age can reduce colorectal cancer by detecting asymptomatic lesions (Center et al., 2009). Although there are differences in the etiologies and epidemiology of colon and rectal cancer (Giovannucci & Wu, 2006), the majority of the studies chose to examine colon and rectum cancers combined. However, a better understanding of these diseases nowadays, shows that these differences have an important impact in their approaches. First of all, the location of the tumours may determines different locations of metastisation. Unlike colon cancers, distal rectal tumours may first metastasize to the lungs because the inferior rectal veins drain into the inferior vena cava rather than into the portal venous system. The histological type can also vary. The vast majority of colorectal tumours are adenocarcinomas but 11-17% are mucinous carcinomas. This type, which has a penchant for the rectum and sigmoid colon, tends to be present at a more advanced stage (Consorti et al., 2000). The carcinoid tumours have a different clinical presentation too, depending on whether they appear in the rectum or in the colon (Marshall & Badnarchuk 1993; Spread et al., 1994). The rectum carcinoids develop at a young age, most of which are less than 2 cm and tend to be indolent. In contrast, colonic carcinoid tumours can be clinically aggressive and often metastise. With a more accurate review, we can see that many habits could influence the development of rectal cancers and not colon cancers. Some studies support the view that family history, as well as the level of physical activity, is a stronger contributor to colon cancer relative to rectal cancer (Wei et al., 2004). The Women’s Health Initiative (a large cohort study) (Paskett et al., 2007) also found a significant link between active cigarette smoking (not passive exposure to cigarette smoke) and rectal but not colon cancer. These differences are important in terms of monitoring and have implications in treatment options, as well. Compared to colon cancers, the sensitivity of CT scan for detection of
Regulation of phenotypic variability by a threshold-based mechanism underlies bacterial persistence

In the face of antibiotics, bacterial populations avoid extinction by harboring a subpopulation of dormant cells that are largely drug insensitive. This phenomenon, termed “persistence,” is a major obstacle for the treatment of a number of infectious diseases. The mechanism that generates both actively growing as well as dormant cells within a genetically identical population is unknown. We present a detailed study of the toxin–antitoxin module implicated in antibiotic persistence of Escherichia coli. We find that bacterial cells become dormant if the toxin level is higher than a threshold, and that the amount by which the threshold is exceeded determines the duration of dormancy. Fluctuations in toxin levels above and below the threshold result in coexistence of dormant and growing cells. We conclude that toxin–antitoxin modules in general represent a mixed network motif that can serve to produce a subpopulation of dormant cells and to supply a mechanism for regulating the frequency and duration of growth arrest. Toxin–antitoxin modules thus provide a natural molecular design for implementing a bet-hedging strategy.
Monitoring of sympathetic tone to assess postoperative pain: skin conductance vs surgical stress index

The number of fluctuations in skin conductance per second has been described as a potential tool for monitoring postoperative pain. More recently, the surgical stress index has shown promising correlations with intra‐operative painful stimuli. We compared both methods for their ability to assess postoperative pain, in 100 postoperative patients who were also asked to quantify their level of pain at different time points in the recovery room. The number of fluctuations per second and surgical stress index were significantly different between pain scoring ≤ 5/10 and > 5/10 on a numeric rating scale (mean (SE) number of fluctuations per second 0.12 (0.02) vs 0.21 (0.03), respectively; p = 0.017, and surgical stress index 57 (1.4) vs 64 (1.9) points, respectively; p = 0.001). Both number of fluctuations in skin conductance per second and surgical stress index identified timepoints with moderate to severe pain with only moderate sensitivity and specificity.
Contact and stigma toward mental illness: Measuring the effectiveness of two video interventions

Researchers have demonstrated that mental illness stigma is both prevalent in our society and has serious negative consequences for mentally ill persons and their friends and family (Corrigan, 2004a). One of the ways researchers have found to reduce mental health stigma is through contact with persons with mental illness (Corrigan et al., 2002; Desforges et al., 1991; Schulze, Richter-Werling, & Angermeyer, 2003). Researchers have also shown that indirect methods of contact, such as videos, can be both effective in reducing stigma toward mental illness and in reaching large groups of individuals (Reinke, Corrigan, Leonhard, Lundin, & Kubiak, 2004). The goal of the current study is to assess the impact of two different video interventions involving indirect contact with persons with mental illness on reducing stigma. The first focused on personal stories of those experiencing mental illness. The second focused on the stories of friends and family members in their support of those experiencing mental illness. The two treatment videos were compared at three time points (pre-test, post-test, and follow-up) to a control video. Participants were 319 undergraduates at a large mid-western university. Results using mixed model Analysis of Variance (ANOVA) indicated the treatment interventions did not significantly impact stigma toward mental illness when compared to the control condition, though, all videos led to some short-term changes in stigma. Future studies aimed at reducing stigma may want to more closely examine the necessary ingredients associated with changing stigma when using a video intervention.
Critical role of DNAX accessory molecule-1 (DNAM-1) in the development of acute graft-versus-host disease in mice

Acute graft-versus-host disease (GVHD) is a life-threatening complication following bone marrow transplantation; however, no effective molecular-targeting therapy has been determined. Here, we show that mice that received allogeneic splenocytes deficient in DNAX accessory molecule-1 (DNAM-1) had significantly milder GVHD and lower mortality than those that received allogeneic WT splenocytes. Donor CD8+ T cells deficient in DNAM-1 showed significantly less proliferation and infiltration of the liver and intestines of recipient mice and produced less IFN-γ after coculture with allogeneic splenocytes than WT CD8+ T cells. Mice prophylactically treated with an anti–DNAM-1 antibody showed milder GVHD and lower mortality than those treated with a control antibody. Moreover, treatment with a single administration of the antibody after the overt onset of GVHD ameliorated GVHD and prolonged survival. Finally, we show that the anti–DNAM-1 antibody therapy also ameliorated the overt GVHD in lethally irradiated mice after MHC-matched, minor antigen-mismatched bone marrow transplantation. These results indicate that DNAM-1 plays an important role in the development of GVHD and is an ideal molecular target for therapeutic approaches to GVHD.