Reflections On Contributing To “Big Discoveries” About The Fly Clock: Our Fortunate Paths As Post-Docs With 2017 Nobel Laureates Jeff Hall, Michael Rosbash, And Mike Young

In the early 1980s Jeff Hall and Michael Rosbash at Brandeis University and Mike Young at Rockefeller University set out to isolate the period (per) gene, which was recovered in a revolutionary genetic screen by Ron Konopka and Seymour Benzer for mutants that altered circadian behavioral rhythms. Over the next 15 years the Hall, Rosbash and Young labs made a series of groundbreaking discoveries that defined the molecular timekeeping mechanism and formed the basis for them being awarded the 2017 Nobel Prize in Physiology or Medicine. Here the authors recount their experiences as post-docs in the Hall, Rosbash and Young labs from the mid-1980s to the mid-1990s, and provide a perspective of how basic research conducted on a simple model system during that era profoundly influenced the direction of the clocks field and established novel approaches that are now standard operating procedure for studying complex behavior

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Impact of the home literacy environment on the L1 reading frequencies of Thai university students: Implications for the learning of an L2

In the Information Age, reading is a critical skill for accessing information and updating skills. However, reluctant readership in L1 may prevent many societies from fully participating in the global community. This reluctance to read may also slow the acquisition of an L2 such as English. This paper will present the findings of an MA dissertation which investigated pleasure reading rates in L1 at a Thai university, to understand better the issue of reluctant readership in L2. Results from a survey of six hundred students found that the home literacy environment may account for some of the differences in students’ L1 reading frequencies. Though the size effects were small, parental reading to children, book ownership, and past reading rates of parents, were all found to have significant associations with students’ present day reading frequencies and attitudes. Implications for SLA theories and reading strategies in the classroom will be discussed, as will the role of schools in promoting literacy

Integrating microfluidic generation, handling and analysis of biomimetic giant unilamellar vesicles

The key roles played by phospholipids in many cellular processes, has led to the development of model systems, to explore both lipid–lipid and lipid–peptide interactions. Biomimetic giant unilamellar vesicles represent close facsimiles of in vivo cellular membranes, although currently their widespread use in research is hindered by difficulties involving their integration into high-throughput techniques, for exploring membrane biology intensively in situ. This paper presents an integrated microfluidic device for the production, manipulation and high-throughput analysis of giant unilamellar vesicles. Its utility is demonstrated by exploring the lipid interaction dynamics of the pore-forming antimicrobial peptide melittin, assessed through the release of fluorescent dyes from within biomimetic vesicles, with membrane compositions similar to mammalian plasma membranes

Contractile stresses in cohesive cell layers on finite-thickness substrates

Using a minimal model of cells or cohesive cell layers as continuum active elastic media, we examine the effect of substrate thickness and stiffness on traction forces exerted by strongly adhering cells. We obtain a simple expression for the length scale controlling the spatial variation of stresses in terms of cell and substrate parameters that describes the crossover between the thin and thick substrate limits. Our model is an important step towards a unified theoretical description of the dependence of traction forces on cell or colony size, acto-myosin contractility, substrate depth and stiffness, and strength of focal adhesions, and makes experimentally testable predictions.Comment: 5 pages, 3 figure

Training Programme Impact in Improving the Working Memory of Students with Learning Disabilities in Reading Arabic

The study aimed to investigate the effect of a training program on improving working memory for students with learning difficulties in reading Arabic. The study sample consisted of (10) students with learning disabilities from Basic Education students from the fifth and sixth grades, and those between the ages (10-11) years as a pilot group and (10) students from the same stage and of the same age as a control group. The researcher used a working memory battery, Raven Test, and a training program he prepared to achieve the study goal. The results showed that there are statistically significant differences in the fields of working memory scale between the members of the experimental and control groups in the dimensional measurement, and in favor of the experimental group to which the training program was applied, by applying the measure of working memory in its three fields. The results also showed that there are statistically significant differences between the pre and post measurements of the areas of the working memory scale in favor of the post application, and for the benefit of the experimental group,This confirms the effectiveness of the training program used. Some recommendations were suggested

Striking circadian neuron diversity and cycling of Drosophila alternative splicing.

Although alternative pre-mRNA splicing (AS) significantly diversifies the neuronal proteome, the extent of AS is still unknown due in part to the large number of diverse cell types in the brain. To address this complexity issue, we used an annotation-free computational method to analyze and compare the AS profiles between small specific groups of Drosophila circadian neurons. The method, the Junction Usage Model (JUM), allows the comprehensive profiling of both known and novel AS events from specific RNA-seq libraries. The results show that many diverse and novel pre-mRNA isoforms are preferentially expressed in one class of clock neuron and also absent from the more standard Drosophila head RNA preparation. These AS events are enriched in potassium channels important for neuronal firing, and there are also cycling isoforms with no detectable underlying transcriptional oscillations. The results suggest massive AS regulation in the brain that is also likely important for circadian regulation

p38 Mitogen-activated Protein Kinase Regulates Oscillation of Chick Pineal Circadian Clock

Extracellular signal-regulated kinase (ERK) and p38 are members of the mitogen-activated protein kinase (MAPK) family, and in some cases these kinases serve for closely related cellular functions within a cell. In a wide range of animal clock structures, ERK plays an important role in the circadian time-keeping mechanism. Here we found that immunoreactivity to p38 protein was uniformly distributed among cells in the chick pineal gland. On the other hand, a constant level of activated p38 was detected over the day, predominantly in the follicular and parafollicular pinealocytes that are potential circadian clock-containing cells. Chronic application of SB203580, a selective and reversible inhibitor of p38, to the cultured chick pineal cells markedly lengthened the period of the circadian rhythm of the melatonin release (up to 28.7 h). Noticeably, despite no significant temporal change of activated p38 level, a 4-h pulse treatment with SB203580 delayed the phase of the rhythm only when delivered during the subjective day. These results indicate a time-of-day-specific role of continuously activated p38 in the period length regulation of the chick pineal clock and suggest temporally separated regulation of the clock by two MAPKs, nighttime-activated ERK and daytime-working p38