The Grammar Comic Book PBL [9th grade]

In the wake of the new state test (EOC/STAAR), students are being commanded not only to write three coherent essays in four hours, but also to employ effective syntax, diction, grammar, and punctuation in their writing. It’s a brilliant ideal that, in reality, more than half of ninth grade students across the state are struggling to meet. The question that surfaces, then, is why are so many students unable to write effectively? And, how can teachers help these struggling students gain the confidence and skills to write well? Most teachers know that in order for students to become good writers, they also need to be good readers. But to become both a good writer and reader, students must understand the basic foundations of the English language: grammar. Grammar—from the basic parts of speech, syntax, diction, to tenses— advances writing, speech, and reading comprehension. It is the building blocks of language, just as DNA is the building block of life; without understanding grammar, we will struggle to understand and correctly employ the English language. Unfortunately, grammar remains a component of English Language Arts curriculum that has been divested and neglected, perhaps because its importance and relevancy has been overlooked and devalued for too many years. But as teachers, we can change that by beginning to weave grammar back into the curriculum. And this grammar unit attempts to do just that

Quantitative Proteomic Analysis of Wheat Cultivars with Differing Drought Stress Tolerance

Using a series of multiplexed experiments we studied the quantitative changes in protein abundance of three Australian bread wheat cultivars (Triticum aestivum L.) in response to a drought stress. Three cultivars differing in their ability to maintain grain yield during drought, Kukri (intolerant), Excalibur (tolerant), and RAC875 (tolerant), were grown in the glasshouse with cyclic drought treatment that mimicked conditions in the field. Proteins were isolated from leaves of mature plants and isobaric tags were used to follow changes in the relative protein abundance of 159 proteins. This is the first shotgun proteomics study in wheat, providing important insights into protein responses to drought as well as identifying the largest number of wheat proteins (1,299) in a single study. The changes in the three cultivars at the different time points reflected their differing physiological responses to drought, with the two drought tolerant varieties (Excalibur and RAC875) differing in their protein responses. Excalibur lacked significant changes in proteins during the initial onset of the water deficit in contrast to RAC875 that had a large number of significant changes. All three cultivars had changes consistent with an increase in oxidative stress metabolism and reactive O2 species (ROS) scavenging capacity seen through increases in superoxide dismutases and catalases as well as ROS avoidance through the decreases in proteins involved in photosynthesis and the Calvin cycle

Early College, Early Success: Early College High School Initiative Impact Study

In 2002, the Bill & Melinda Gates Foundation launched the ECHSI with the primary goal of increasing the opportunity for underserved students to earn a postsecondary credential. To achieve this goal, Early Colleges provide underserved students with exposure to, and support in, college while they are in high school. Early Colleges partner with colleges and universities to offer all students an opportunity to earn an associate's degree or up to two years of college credits toward a bachelor's degree during high school at no or low cost to the students. The underlying assumption is that engaging underrepresented students in a rigorous high school curriculum tied to the incentive of earning college credit will motivate them and increase their access to additional postsecondary education and credentials after high school. Since 2002, more than 240 Early Colleges have opened nationwideThis study focused on the impact of Early Colleges. It addressed two questions:1. Do Early College students have better outcomes than they would have had at other high schools?2. Does the impact of Early Colleges vary by student background characteristics (e.g., gender and family income)? To answer these questions, we conducted a lottery-based randomized experiment, taking advantage of the fact that some Early Colleges used lotteries in their admissions processes. By comparing the outcomes for students who participated in admissions lotteries and were offered enrollment with the outcomes for students who participated in the lotteries but were not offered enrollment, we can draw causal conclusions about the impact of Early Colleges.The primary student outcomes for this study were high school graduation, college enrollment, and college degree attainment. We also examined students' high school and college experiences. Data on student background characteristics and high school outcomes came from administrative records from schools, districts, and states; data on collegeoutcomes came from the National Student Clearinghouse (NSC); and data on high school and college experiences and intermediate outcomes such as college credit accrual camefrom a student surveyWe assessed the impact of Early Colleges on these outcomes for a sample of 10 Early Colleges that did the following:-Enrolled students in grades 9 -- 12 and had high school graduates in the study years (2005 -- 2011)-Used lotteries as part of the admission processes in at least one of the study cohorts (students who entered ninth grade in 2005 -- 06, 2006 -- 07, or 2007 -- 08)-Retained the lottery recordsEight of the 10 Early Colleges in the study were included in the student survey. The overall study sample included 2,458 students and the survey sample included 1,294 students. The study extended through three years past high school

B-Vitamin Intake and Biomarker Status in Relation to Cognitive Decline in Healthy Older Adults in a 4-Year Follow-Up Study

Advancing age can be associated with an increase in cognitive dysfunction, a spectrum of disability that ranges in severity from mild cognitive impairment to dementia. Folate and the other B-vitamins involved in one-carbon metabolism are associated with cognition in ageing but the evidence is not entirely clear. The hypothesis addressed in this study was that lower dietary intake or biomarker status of folate and/or the metabolically related B-vitamins would be associated with a greater than expected rate of cognitive decline over a 4-year follow-up period in healthy older adults. Participants (aged 60–88 years; n = 155) who had been previously screened for cognitive function were reassessed four years after initial investigation using the Mini-Mental State Examination (MMSE). At the 4-year follow-up assessment when participants were aged 73.4 ± 7.1 years, mean cognitive MMSE scores had declined from 29.1 ± 1.3 at baseline to 27.5 ± 2.4 (p < 0.001), but some 27% of participants showed a greater than expected rate of cognitive decline (i.e., decrease in MMSE > 0.56 points per year). Lower vitamin B6 status, as measured using pyridoxal-5-phosphate (PLP; <43 nmol/L) was associated with a 3.5 times higher risk of accelerated cognitive decline, after adjustment for age and baseline MMSE score (OR, 3.48; 95% CI, 1.58 to 7.63; p < 0.05). Correspondingly, lower dietary intake (0.9–1.4 mg/day) of vitamin B6 was also associated with a greater rate of cognitive decline (OR, 4.22; 95% CI, 1.28–13.90; p < 0.05). No significant relationships of dietary intake or biomarker status with cognitive decline were observed for the other B-vitamins. In conclusion, lower dietary and biomarker status of vitamin B6 at baseline predicted a greater than expected rate of cognitive decline over a 4-year period in healthy older adults. Vitamin B6 may be an important protective factor in helping maintain cognitive health in ageing

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Abstract: Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target

The genomic landscape of colorectal cancer (CRC) is shaped by inactivating mutations in tumour suppressors such as APC, and oncogenic mutations such as mutant KRAS. Here we used genetically engineered mouse models, and multimodal mass spectrometry-based metabolomics to study the impact of common genetic drivers of CRC on the metabolic landscape of the intestine. We show that untargeted metabolic profiling can be applied to stratify intestinal tissues according to underlying genetic alterations, and use mass spectrometry imaging to identify tumour, stromal and normal adjacent tissues. By identifying ions that drive variation between normal and transformed tissues, we found dysregulation of the methionine cycle to be a hallmark of APC-deficient CRC. Loss of Apc in the mouse intestine was found to be sufficient to drive expression of one of its enzymes, adenosylhomocysteinase (AHCY), which was also found to be transcriptionally upregulated in human CRC. Targeting of AHCY function impaired growth of APC-deficient organoids in vitro, and prevented the characteristic hyperproliferative/crypt progenitor phenotype driven by acute deletion of Apc in vivo, even in the context of mutant Kras. Finally, pharmacological inhibition of AHCY reduced intestinal tumour burden in ApcMin/+ mice indicating its potential as a metabolic drug target in CRC

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead