Reprogramming within Hours Following Nuclear Transfer into Mouse but not Human Zygotes

Fertilized mouse zygotes can reprogram somatic cells to a pluripotent state. Human zygotes might therefore be useful for producing patient-derived pluripotent stem cells. However, logistical, legal and social considerations have limited the availability of human eggs for research. Here we show that a significant number of normal fertilized eggs (zygotes) can be obtained for reprogramming studies. Using these zygotes, we found that when the zygotic genome was replaced with that of a somatic cell, development progressed normally throughout the cleavage stages, but then arrested before the morula stage. This arrest was associated with a failure to activate transcription in the transferred somatic genome. In contrast to human zygotes, mouse zygotes reprogrammed the somatic cell genome to a pluripotent state within hours after transfer. Our results suggest that there may be a previously unappreciated barrier to successful human nuclear transfer, and that future studies could focus on the requirements for genome activation.Stem Cell and Regenerative Biolog

Deweyan tools for inquiry and the epistemological context of critical pedagogy

This article develops the notion of resistance as articulated in the literature of critical pedagogy as being both culturally sponsored and cognitively manifested. To do so, the authors draw upon John Dewey\u27s conception of tools for inquiry. Dewey provides a way to conceptualize student resistance not as a form of willful disputation, but instead as a function of socialization into cultural models of thought that actively truncate inquiry. In other words, resistance can be construed as the cognitive and emotive dimensions of the ongoing failure of institutions to provide ideas that help individuals both recognize social problems and imagine possible solutions. Focusing on Dewey\u27s epistemological framework, specifically tools for inquiry, provides a way to grasp this problem. It also affords some innovative solutions; for instance, it helps conceive of possible links between the regular curriculum and the study of specific social justice issues, a relationship that is often under-examined. The aims of critical pedagogy depend upon students developing dexterity with the conceptual tools they use to make meaning of the evidence they confront; these are background skills that the regular curriculum can be made to serve even outside social justice-focused curricula. Furthermore, the article concludes that because such inquiry involves the exploration and potential revision of students\u27 world-ordering beliefs, developing flexibility in how one thinks may be better achieved within academic subjects and topics that are not so intimately connected to students\u27 current social lives, especially where students may be directly implicated

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Accelerating the in vitro emulation of Alzheimer’s disease-associated phenotypes using a novel 3D blood-brain barrier neurosphere co-culture model

High failure rates in clinical trials for neurodegenerative disorders such as Alzheimer’s disease have been linked to an insufficient predictive validity of current animal-based disease models. This has created an increasing demand for alternative, human-based models capable of emulating key pathological phenotypes in vitro. Here, a three-dimensional Alzheimer’s disease model was developed using a compartmentalized microfluidic device that combines a self-assembled microvascular network of the human blood-brain barrier with neurospheres derived from Alzheimer’s disease-specific neural progenitor cells. To shorten microfluidic co-culture times, neurospheres were pre-differentiated for 21 days to express Alzheimer’s disease-specific pathological phenotypes prior to the introduction into the microfluidic device. In agreement with post-mortem studies and Alzheimer’s disease in vivo models, after 7 days of co-culture with pre-differentiated Alzheimer’s disease-specific neurospheres, the three-dimensional blood-brain barrier network exhibited significant changes in barrier permeability and morphology. Furthermore, vascular networks in co-culture with Alzheimer’s disease-specific microtissues displayed localized β-amyloid deposition. Thus, by interconnecting a microvascular network of the blood-brain barrier with pre-differentiated neurospheres the presented model holds immense potential for replicating key neurovascular phenotypes of neurodegenerative disorders in vitro

Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

UPAYA MENINGKATKAN MOTIVASI BELAJAR SISWA MELALUI MEDIA GAME EDUCATION DALAM PEMBELAJARAN IPS DI MTs HASBUR RACHMAN ALIF DESA LENGKONG WETAN KABUPATEN MAJALENGKA

ASEP SAMSUL MA'ARIF : Berdasarkan Observasiawal di kelas VII MTs Hasbur Rachman Alif terlihat proses pembelajaran IPS masih menggunakan media spidol dan papan tulis. Sehingga banyak siswa yang kurang memperhatikan guru pada saat proses pembelajaran., Hal ini berakibat pada kejenuhan dan kebosanan yang berdampak pada hasil belajar siswa yang kurang dari KKM yang diterapkan di MTs Hasbur Rachman Alif yakni 70. Tujuan penelitian ini untuk mengetahui bagaimana penerapan pembelajaran dengan menggunakan media Game Education pada mata pelajaran IPS Terpadu, aktivitas siswa dan kinerja guru dengan pembelajaran dengan menggunakan media Game Education, dan mengetahui motivasi belajar siswa sebelum dan setelah diterapkannya pembelajaran dengan menggunakan media Game education pada mata pelajaran IPS Terpadu di MTs Hasbur Rachman Alif. Pembelajaran dengan menggunakan media Game Education menekankan motivasi siswa untuk berpikir kritis dan menuangkan. Hal ini memudahkan siswa untuk mengakses materi IPS yang banyak dimanapun, serta mempemudah daya ingat siswa tentang apayatgtelah didapatkan selama proses pembelajaran. Penelitian ini menggunakan Penelitian Tindakan Kelas (pTK) yang dilaksanakan selama tiga siklus. Teknik Pengumpulan data menggunakan observasi, tes, dan dokumentasi. Subjek penelitian ini adalah siswa kelas VII MTs Hasbur Rachman Alif sebanyak 31 siswa yang terdiri dari 18 siswa laki-laki dan 13 siswa perempuan. Pembelajaran dengan menggunakan media Game Education dapat meningkatkan motivasi belajar siswa hal ini terlihat dari hasil tes yang telah dilakukan selama tiga siklus, dimana pada pratindakan (pretes) nilai sebesar 65,25 dan ketuntasan belajar 25 yo, siklus I nilai rata-rata sebesar 76,75 dan ketuntasan_ belajar siswa sebesar 65,5%o siklus II nilai rata-rata siswa 85,75 dan nilai ketuntasan belajar sebesar 90% siklus III dengan nilai rata-rata 92,25 dan ketuntasan belajar mengalami peningkatanya itu 97,5yo. Dengan demikian dapat disimpulkan bahwa pembelajaran dengan menggunakan media Game Education merupakan salah satu upaya untuk meningkatkan hasil belajar siswa pada mata pelajaran IPS Terpadu di MTs Hasbur Rachman Alif. Kata Kunci: Game Education, MotivasiBelajar, PTK

Suppression of ψ(2S) production in p-Pb collisions at √sNN=5.02 TeV .

The ALICE Collaboration has studied the inclusive production of the charmonium state ψ(2S) in proton-lead (p-Pb) collisions at the nucleon-nucleon centre of mass energy √sNN = 5.02TeV at the CERN LHC. The measurement was performed at forward (2.03 < ycms < 3.53) and backward (−4.46 < ycms < −2.96) centre of mass rapidities, studying the decays into muon pairs. In this paper, we present the inclusive production cross sections σ (2S), both integrated and as a function of the transverse momentum pT, for the two ycms domains. The results are compared to those obtained for the 1S vector state (J/ψ), by showing the ratios between the production cross sections, as well as the double ratios [σ (2S)/σJ/ ]pPb/[σ (2S)/σJ/ ]pp between p-Pb and proton-proton collisions. Finally, the nuclear modification factor for inclusive ψ(2S) is evaluated and compared to the measurement of the same quantity for J/ψ and to theoretical models including parton shadowing and coherent energy loss mechanisms. The results show a significantly larger suppression of the ψ(2S) compared to that measured for J/ψ and to models. These observations represent a clear indication for sizeable final state effects on ψ(2S) production

Production of charged pions, kaons and protons at large transverse momenta in pp and Pb-Pb collisions at sNN\sqrt{s_{NN}} = 2.76 TeV

Transverse momentum spectra of $\pi^{\pm}, K^{\pm}$ and $p(\bar{p})$ up to $p_T$ = 20 GeV/c at mid-rapidity, |y| $\le$ 0.8, in pp and Pb-Pb collisions at $\sqrt{s_{NN}}$ = 2.76 TeV have been measured using the ALICE detector at the LHC. At intermediate $p_T$ (2-8 GeV/c) an enhancement of the proton-to-proton ratio, (p + \bar{p})/(\pi^+ + \pi^-\(), with respect to pp collisions is observed and the ratio reaches 0.80 in central Pb-Pb collisions. The measurement of the nuclear modification factors for \(\pi^{\pm}, K^{\pm} and $p(\bar{p})$ indicates that within the systematic and statistical uncertainties they are the same at high $p_T$ (> 10 GeV/c), suggesting that the chemical composition of leading particles from jets in the medium is similar to that of vacuum jets.publishedVersio