Miracle-dz/UniFAR-FTUs huggingface dataset:
A Signature in HIV-1 Envelope Leader Peptide Associated with Transition from Acute to Chronic Infection Impacts Envelope Processing and Infectivity

Mucosal transmission of the human immunodeficiency virus (HIV) results in a bottleneck in viral genetic diversity. Gnanakaran and colleagues used a computational strategy to identify signature amino acids at particular positions in Envelope that were associated either with transmitted sequences sampled very early in infection, or sequences sampled during chronic infection. Among the strongest signatures observed was an enrichment for the stable presence of histidine at position 12 at transmission and in early infection, and a recurrent loss of histidine at position 12 in chronic infection. This amino acid lies within the leader peptide of Envelope, a region of the protein that has been shown to influence envelope glycoprotein expression and virion infectivity. We show a strong association between a positively charged amino acid like histidine at position 12 in transmitted/founder viruses with more efficient trafficking of the nascent envelope polypeptide to the endoplasmic reticulum and higher steady-state glycoprotein expression compared to viruses that have a non-basic position 12 residue, a substitution that was enriched among viruses sampled from chronically infected individuals. When expressed in the context of other viral proteins, transmitted envelopes with a basic amino acid position 12 were incorporated at higher density into the virus and exhibited higher infectious titers than did non-signature envelopes. These results support the potential utility of using a computational approach to examine large viral sequence data sets for functional signatures and indicate the importance of Envelope expression levels for efficient HIV transmission.
Concordant expression of KChIP2 mRNA, protein and transient outward current throughout the canine ventricle

Expression of the transient outward K+ current (Ito) was analysed in nine different regions of the canine ventricle. In addition to the previously described transmural gradients in the right and left ventricular free walls, an inverted U‐shaped pattern of Ito expression was observed in the interventricular septum. The mRNA and protein expression for the K+ channel β subunit KChIP2 were examined in the same tissues. The KChIP2 protein levels closely matched mRNA expression in all regions of the ventricle and paralleled the density of Ito. The global pattern of gene expression in human epicardial and endocardial tissue was examined using microarrays. Only 0.1 % of the genes expressed in the human ventricle displayed the same expression pattern as the KChIP2 gene in left ventricle. It is unlikely, therefore, that the reported distribution of KChIP2 protein within the ventricle can be explained by a cross‐reaction of the anti‐KChIP2 antibody with a different protein. It is concluded that transcriptional regulation of the KChIP2 gene is a primary determinant of Ito expression in heart.
Improved human tenocyte proliferation and differentiation in vitro by optimized silk degumming

Tendon disorders are common clinical conditions. Tendon tissue engineering provides a new approach for tendon repair by integrating engineered substitutes with their native counterparts. Silk is considered to be a promising candidate for tendon engineering because of its biological and mechanical properties. However, a major concern with using silk for biomedical applications is the immune responses generated by sericin, a glue-like protein that coats the silk fibres. This study improves the existing protocols for silk ‘degumming’ which removes sericin and enables preparation of silk that is suitable for tendon regeneration. Bombyx mori silks were treated by sequential treatments with different proteases. The efficiency of degumming was determined by measuring weight loss, picric acid and carmine staining and scanning electron microscopy. To evaluate the cellular responses after degumming, the growth and differentiation of human tenocytes on silks were examined. The results showed that sequential protease treatment effectively degummed raw silks. The sequentially degummed silks showed enhanced tenocyte proliferation and upregulated mRNA levels of tendon markers. Thick cell multilayers formed on the treated silks, with cells and collagen fibres penetrating into the spaces in individual silk filaments, resulting in a structure resembling human tendon.
Regional Gray Matter Volume Is Associated with Empathizing and Systemizing in Young Adults

Empathizing is defined as the drive to identify the mental states of others for predicting their behavior and responding with an appropriate emotion. Systemizing is defined as the drive to analyze a system in terms of the rules that govern the system in order to predict its behavior. Using voxel-based morphometry and questionnaires in a large sample of normal, right-handed young adults, we investigated the regional gray matter volume (rGMV) correlates of empathizing and systemizing and additionally those of the D score, which is the difference between systemizing and empathizing, to reveal the comprehensive picture of those correlates. Negative rGMV correlates of empathizing and positive rGMV correlates of the D score (formed by the negative correlation between rGMV and empathizing), were found primarily in nodes in the default mode network, mirror neuron system, dorsal anterior cingulate cortex, and the lateral part of the prefrontal cortex together with other areas. Positive rGMV correlates of systemizing and of the D score (formed by the positive correlation between rGMV and systemizing) were found primarily in nodes in the external attention system, middle cingulate cortex, and other regions. Negative rGMV correlates of systemizing were found in an area close to the left posterior insula and putamen. These findings reconcile some previously inconsistent findings, provide other new findings and suggest that these areas contribute to empathizing–systemizing. Furthermore, the negative/positive rGMV correlates of empathizing and positive/negative rGMV correlates of systemizing overlapped substantially. This may be in line with the notion that empathizing and systemizing compete neurally in the brain.
The Founding Myths of Israel: Nationalism, Socialism, and the Making of the Jewish State

The Muslim Brothers and the Palestine Question: 1928-1947, by Abd Al-Fattah Muhammad El-Awaisi. New York: I.B. Tauris, 1998. xiv + 210 pages. Notes to p. 257. Bibl. to p. 269. Index to p. 274. $59.50. Reviewed by Hanna Y. Freij A plethora of books and articles about Islamic movements that focus on the ideology, activities and so-called "threats to the western world. " This book is a detailed study of the Muslim Brothers Society's (al-Ikhwan al-Muslimin) "attitude towards the Palestine question.based on its own philosophy, concepts and aims" (p. x). The title accurately reflects what the book is about. The author has done an admirable job researching the subject; sources include various publications of the Muslim Brothers, interviews with contemporaries of Hasan al-Banna' and British Foreign Office documents. The book is divided into three parts. The first focuses on the role of propaganda, the second on military preparations, and the third on the beginnings of the armed struggle. The essence of the book, and its most revealing feature, is found in the section dealing with the Muslim Brothers' propaganda machine, and its use on behalf of the Palestine question. From their inception, the Muslim Brothers have had a dual-national as well as transnationalidentity. Their transnational identity crystallized during their campaign in Egypt on behalf of the Palestine Revolt of 1936-39. After the 1935 "martyrdom" of the Islamist leader, 'Izz al-Din al-Qassam, the Muslim Brothers further consolidated their propaganda campaign in Egypt. However, the author shows convincingly that, during the early period under examination, Egyptian nationalism was by far the most salient badge of identity among Egyptians. He cites Ahmad Lutfi al-Sayyid's statement that "an Egyptian is one who does not identify himself with any nation but Egypt.Our nationalism directs our desires towards our nation.and our nation alone" (p. 22); hence, the Ikhwan had an uphill battle. The Ikhwan used the mosque and their magazine, al-Nadhir, to foment opposition both to the British and to the passive attitude of the Egyptian government (pp.48-49). They aroused significant interest among the Egyptian public in the Islamic fraternity by urging them to participate in the jihad (p. 97). One of the main targets of the propaganda campaign was the Jewish community in Egypt, who, through its press, had encouraged all types of ties between its members and Jews living in Palestine (p. 69). The Ikhwan targeted Jewish businesses in Egypt as harmful to Egyptians, and declared that the establishment of a Jewish state in Palestine would be "an insult to Muslims on their own doorstep" (p. 72). Through the massive propaganda campaign, which was assisted financially by the Mufti of Jerusalem, the Ikhwan finally managed to extract a supportive speech for Palestine from the government of Muhammad Mahmud. …
Exercise training in COPD: What is it about intensity?

Most of the current guidelines for pulmonary rehabilitation recommend higher, over lower, intensity exercise training for COPD. Typically, we consider intensity of exercise training to be a key component of any exercise training programme. Whilst studies of young individuals have demonstrated that higher exercise training intensity results in greater improvements in exercise capacity, the evidence for older patients is not so clear cut. In COPD, there is limited evidence regarding the optimal intensity of exercise training. Using both physiological (peak exercise capacity) and patient‐centred (e.g. quality of life) outcomes, it remains inconclusive if higher intensity exercise training bestows any greater benefit than low‐intensity exercise. If we examine the data from interval training studies, which used both high‐ and low‐intensity interval and continuous exercise, we are able to generate more data for comparison. Unfortunately, these data are challenging to interpret due to heterogeneity in how interval training was prescribed. However, when we normalize the interval training data for training volume and examine the change in peak cycling power, there is a relationship between training intensity and increase in peak power (Wpeak, r = 0.68, P < 0.05). Hence, whilst there is an inconclusive amount of evidence to support this intervention based on studies that only examined high‐ versus low‐intensity continuous exercise, the additional data from interval training studies would suggest that higher intensity may be superior in terms of increases in Wpeak. Future studies should focus on establishing a threshold and an optimal training intensity for COPD.
Influences of L2 affective variables on willingness to communicate in English

As globalization advances, English education in Japan has increasingly been given importance. Though unlike an ESL situation where learners are required to use English in their everyday life, Japan is in an EFL context where people do not usually have many opportunities to speak English. This means that the majority of English learners in Japan can only use English in limited situations, such as English classrooms. However, to improve one's level of spoken English, it is important to use English; as MacIntyre and Charos (1996) said that, “One must talk to learn. ” Swain (1985) also emphasizes the importance of the role of output to develop speech in L2. Therefore, having a sense of willingness to communicate in L2 (L2 WTC) becomes a very important factor in improving L2 speaking skills. L2 learners with a high WTC are more likely to place themselves in L2 communicative acts more often (MacIntyre et al., 1998). Empirical studies also reported that WTC led to the actual use of L2 (Clément et al., 2003; Hashimoto, 2002) as well as L2 speaking proficiency (Yoshikawa, 2005). In this study, I examined the structural relationships among the L2 affective variables that affect the L2 WTC of 311 Japanese university students majoring in engineering.
Student expectations and the effect of experience

Bob Pithers Faculty of Education – University of Technology, Sydney. & Tony Holland Faculty of Education – University of Technology, Sydney. Abstract One aspect of empowering students at a university is to take the current view that they are now to be regarded as “clients” or “customers” rather than recipients of education. In this context it is imperative that student demands and expectations of lecturing staff have been given little considered when planning, designing and delivering courses. This of course makes the assumption that university students are an homogenous groups with respect to their expectations. This study surveyed students to find out whether this assumption is tenable or if student expectation change over the course of study. With this objective in mind this study surveyed two students groups: one group fresh from high school and a second group in their last year of study,
Flagellin, a Novel Mediator of Salmonella-Induced Epithelial Activation and Systemic Inflammation: IκBα Degradation, Induction of Nitric Oxide Synthase, Induction of Proinflammatory Mediators, and Cardiovascular Dysfunction1

Gram-negative sepsis is mediated by the actions of proinflammatory genes induced in response to microbes and their products. We report that flagellin, the monomeric subunit of flagella, is a potent proinflammatory species released by Salmonella. Flagellin (1 μg/ml) induces IκBα degradation, NF-κB nuclear translocation, and inducible NO synthase expression in cultured intestinal epithelial cells (IEC). Aflagellic Salmonella mutants do not induce NF-κB activation or NO production by cultured IEC. Antiserum to flagellin blocks NO production in IEC induced by medium conditioned by a variety of motile Gram-negative enteric pathogens (Escherichia coli, Salmonella muenchen, Serratia marcescens, Proteus mirabilis, and Proteus vulgaris). Flagellin, when injected systemically (∼10 μg/mouse), induces systemic inflammation characterized by the systemic expression of a range of proinflammatory cytokines and chemokines and of inducible NO synthase. At higher doses (∼300 μg/mouse), flagellin induces shock, characterized by hypotension, reduced vascular contractility in mice, and death. The effects of flagellin do not diminish in C3H/HeJ LPS-resistant mice, indicating that the Toll-like receptor-4 receptor is not involved in flagellin’s actions. In LPS-resistant mice, i.p. injection of S. dublin flagellin or medium conditioned by wild-type S. dublin induces serum IFN-γ and TNF-α, whereas medium conditioned by aflagellic mutants has no effect. Flagellin can be detected in the blood of rats with septic shock induced by live bacteria at approximately 1 μg/ml. We propose that flagellin released by Gram-negative pathogens may contribute to the inflammatory response by an LPS- and Toll-like receptor-4-independent pathway.
Nedocromil sodium and astemizole, alone or combined, in the treatment of seasonal allergic conjunctivitis

Abstract Two hundred and seven patients with active symptoms of allergic conjunctivitis were studied in a four‐week multicentre double blind, double dummy, clinical trial comparing efficacy and safety of nedocromil sodium eye drops with oral astemizole, placebo, and the combined active treatments. Clinical signs were evaluated by clinicians after 1, 2 and 4 weeks, while symptoms were recorded by patients on daily diary cards. Overall opinions were recorded at the end of treatment. Nedocromil sodium eye drops and astemizole, alone or combined, significantly reduced ocular symptoms when compared to placebo (diary card total symptom score and patients' opinion). In the clinicians' opinion nedocromil sodium alone or combined (but not astemizole alone) significantly decreased ocular symptoms when compared to placebo. All treatments were safe and well tolerated, drowsiness being the most frequent side effect observed in patients treated with astemizole. These results indicate the effectiveness of nedocromil sodium eye drops in the treatment of seasonal allergic conjunctivitis.
TherapyCytotoxicity in a Model of Anti-Lymphoma Promotes Antibody-Dependent Cellular Blocking NK Cell Inhibitory Self-Recognition

Human NK cells lyse Ab-coated target cells through the process of Ab-dependent cellular cytotoxicity (ADCC). Improving ADCC responses is desirable because it is thought to be an important antitumor mechanism for some Abs. NK cell inhibitory receptors, such as killer cell Ig-like receptors, engage with MHC class I molecules on self-cells to block NK cell activation. Accordingly, we enhanced ADCC responses by blocking NK cell inhibitory receptors, thus perturbing induction of the self-recognition signal. In a cell line model of anti-lymphoma therapy, the combination of rituximab with an Ab that blocks inhibitory self-recognition yielded increased NK cell-mediated target cell lysis when compared with rituximab alone. To validate this proof-of-concept, we then used a more representative approach in which an individual’s fresh primary NK cells encountered autologous, EBV-trans-formed B cells. In this system, rituximab and a combination of Abs that block NK cell inhibitory receptors yielded improved NK cell-mediated lysis over rituximab alone. The results show, for the ﬁrst time, that disruption of inhibitory self-recognition can efﬁciently promote ADCC in a human model, applying an autologous system in which physiologic checkpoints are in place. This method provides an alternative approach to potentiate the therapeutic beneﬁt of antitumor Abs that mediate ADCC. The Journal of Immunology, 2008, 180: 6392–6401. the CD16 gene using Lipofectamine Plus reagent (Life Tech- nologies). Supernatants of these transfected cells grown in serum-free Opti-MEM medium (Life Technologies) for 2 days cocultured with NK-92 or NK-92.26. 5 cell lines fo r 8 h in thepresence of Lipofectamine Plus reagent. (cid:3) -MEM IL-2 days. time of NK cells efﬁciently GFP FACSVantage ﬂow cytometer (BD Chase Center
Using videotaped extracts of lessons during interviews to facilitate the eliciting of teachers' thinking. An example with music schoolteachers' perceptions of creativity

This paper explores methodological issues regarding the eliciting of teachers' views regarding creativity, with particular reference to the use of videotaped extracts of lessons during in-depth semi-structured interviews. The paper draws on a doctoral study focussed on English music schoolteachers' perceptions of creativity. Various research designs and results from previous studies were examined and the implications highlighted (Odena, 2001a). A qualitative research design was piloted with three teachers and subsequently refined (Odena, 2001b). It was then used to allow six final participants to reflect on their own ideas. Between three to five hours of music lessons on composition and improvisation were observed and videotaped for each teacher. Final interviews with participants were transcribed and the process of analysis was assisted by a software package for qualitative research (i.e. NVivo). The study exemplified the complexities in defining the term ‘creativity’. It is suggested that the use of videotaped extracts of lessons for the purpose of discussion with participants during the interviews, proved beneficial in exploring the teachers' perceptions. This method may have relevance for both researchers and practitioners interested in teachers' attitudes.
Recruitment of Mediator Complex by Cell Type and Stage-Specific Factors Required for Tissue-Specific TAF Dependent Gene Activation in an Adult Stem Cell Lineage

Onset of terminal differentiation in adult stem cell lineages is commonly marked by robust activation of new transcriptional programs required to make the appropriate differentiated cell type(s). In the Drosophila male germ line stem cell lineage, the switch from proliferating spermatogonia to spermatocyte is accompanied by one of the most dramatic transcriptional changes in the fly, as over 1000 new transcripts turn on in preparation for meiosis and spermatid differentiation. Here we show that function of the coactivator complex Mediator is required for activation of hundreds of new transcripts in the spermatocyte program. Mediator appears to act in a sequential hierarchy, with the testis activating Complex (tMAC), a cell type specific form of the Mip/dREAM general repressor, required to recruit Mediator subunits to the chromatin, and Mediator function required to recruit the testis TAFs (tTAFs), spermatocyte specific homologs of subunits of TFIID. Mediator, tMAC and the tTAFs co-regulate expression of a major set of spermatid differentiation genes. The Mediator subunit Med22 binds the tMAC component Topi when the two are coexpressed in S2 cells, suggesting direct recruitment. Loss of Med22 function in spermatocytes causes meiosis I maturation arrest male infertility, similar to loss of function of the tMAC subunits or the tTAFs. Our results illuminate how cell type specific versions of the Mip/dREAM complex and the general transcription machinery cooperate to drive selective gene activation during differentiation in stem cell lineages.
Could African and Low- and Middle-Income Countries Contribute Scientifically to Global Cancer Care?

Could African countries, as exemplars of low- and middle-income countries (LMICs), make scientific contributions that would increase the affordability of cancer care globally? After four decades of effort to improve the quality of care, Robert Brook, a distinguished expert on quality, declared in 2010 “The end of the quality improvement movement: long live improving value! ” 1 “Value” is broadly defined as outcomes relative to the total costs of care and encompasses effectiveness, cost-effectiveness, efficiency, quality, safety, and quality of life. 1-3 Value is relevant to cancer care in both developed and developing countries. 1 Better value care does not mean inferior care. Economic studies and measures such as cost reduction without regard to the outcomes achieved are dangerous and can lead to false savings and potentially limit effective care. 2,3
Extensive Direct Subcortical Cerebellum-Basal Ganglia Connections in Human Brain as Revealed by Constrained Spherical Deconvolution Tractography

The connections between the cerebellum and basal ganglia were assumed to occur at the level of neocortex. However evidences from animal data have challenged this old perspective showing extensive subcortical pathways linking the cerebellum with the basal ganglia. Here we tested the hypothesis if these connections also exist between the cerebellum and basal ganglia in the human brain by using diffusion magnetic resonance imaging and tractography. Fifteen healthy subjects were analyzed by using constrained spherical deconvolution technique obtained with a 3T magnetic resonance imaging scanner. We found extensive connections running between the subthalamic nucleus and cerebellar cortex and, as novel result, we demonstrated a direct route linking the dentate nucleus to the internal globus pallidus as well as to the substantia nigra. These findings may open a new scenario on the interpretation of basal ganglia disorders.