Using gain of function genetics to explore the role of non-histone chromosomal protein D1 in Drosophila melanogaster

The organization of eukaryotic genomes requires a harmony between efficient compaction and accessibility. This is achieved through the packaging of chromatin and the influence of chromosomal proteins, a topic not well understood. A chromosomal protein that remains a mystery at present is the D1 protein. Identified in 1974 by Alfageme et al., D1 has been highly characterized but its function remains unknown. The goal of this study was to elucidate the function of D1 by overexpression analysis using the GAL4/UAS system in Drosophila melanogaster. Analysis of gain-of-function phenotypes due to D1 overexpression in a variety of tissues determined that ectopic D1 interfered in the genetic cascades of a number of unrelated processes and in unrelated tissues. In addition, ectopic expression of D1 in the salivary glands led to ectopic associations of the polytene chromosomes resulting in chromosome entanglement. Mapping of the cytological intervals of these ectopic contacts resulted in a strong correlation to the localization of features of intercalary heterochromatin. An additional study indicated that D1 is activated by interaction with protein kinase CK2. I hypothesize overall, based on this study that the phosphoprotein D1, activated by protein kinase CK2, has a role in inducing and/or maintaining heterochromatic properties of the genome by binding to AT-rich satellite and satellite-related DNA in a variety of processes and tissues. The D1 protein, with ten copies of the AT hook binding motif, most likely functions in tandem with other transcription factors as a means of facilitating structural changes to chromatin resulting in the regulation of gene expression.;The D1 protein binds to the 1.688 g/cm3 and 1.672 g/cm 3 satellite repeats of heterochromatin as well as several euchromatic loci. Analysis of D1 cDNA determined the presence of ten copies of the highly conserved AT hook binding motif, a motif hypothesized to participate in facilitating architectural changes in the DNA. D1 mRNA is maternally loaded and highly expressed at the beginning of embryonic development and later in adult gametogenesis. In addition, the D1 protein has been compared to proteins of the mammalian High Mobility Group A family (HMGA), proteins functioning as architectural elements that alter the structure of DNA to produce and enhance various DNA-dependent activities. Even though D1 has been highly studied, its function remains unknown. Elucidating the function of the D1 chromosomal protein may provide intriguing information of the relationship between chromatin structure, gene expression and gene regulation, an understanding that once fully elucidated would revolutionize many fields

On the spin modulated circular polarization from the intermediate polars NY Lup and IGRJ1509-6649

We report on high time resolution, high signal/noise, photo-polarimetry of the intermediate polars NY Lup and IGRJ1509-6649. Our observations confirm the detection and colour dependence of circular polarization from NY Lup and additionally show a clear white dwarf, spin modulated signal. From our new high signal/noise photometry we have unambiguously detected wavelength dependent spin and beat periods and harmonics thereof. IGRJ1509-6649 is discovered to also have a particularly strong spin modulated circularly polarized signal. It appears double peaked through the I filter and single peaked through the B filter, consistent with cyclotron emission from a white dwarf with a relatively strong magnetic field. We discuss the implied accretion geometries in these two systems and any bearing this may have on the possible relationship with the connection between polars and soft X-ray-emitting IPs. The relatively strong magnetic fields is also suggestive of them being polar progenitors.Comment: 8 pages, 6 figures and 1 table. Accepted for publication in MNRA

Vitamin D Levels in Patients with Colorectal Cancer and Matched Household Members.

BackgroundVitamin D levels, as measured by 25-hydroxyvitamin-D [25(OH) D], are inversely related to the risk of developing colorectal cancer (CRC). Given shared demographic and lifestyle factors among members of the same household, we sought to examine vitamin D levels and associated lifestyle factors in household members of CRC patients.MethodsThirty patients with pathologically confirmed CRC were enrolled prior to oncologic therapy along with unrelated household members who were matched for age (+/- 5 years) and race. In addition to serum blood draws for 25(OH)D levels at baseline and six-month follow-up, questionnaires collected gender, vitamin use, body mass index, family history of CRC, race, dietary vitamin D, UV exposure, and exercise.ResultsMedian serum 25(OH) D levels were 26.8 ng/mL for CRC patients versus 27.3 for household members (P=0.89). Vitamin-D associated factors such as dietary vitamin D intake, UV exposure, gender, multivitamin use, vitamin D supplement use, and family history of CRC were not significantly different between CRC patients and paired household members (P>0.05). Household members were more likely than CRC patients to be overweight and to exercise more.ConclusionsVitamin D levels and many associated lifestyle factors were not significantly different between CRC patients and unrelated paired household members. Given comparable vitamin D levels, further investigation into whether age-matched household members of CRC patients may be at increased risk for CRC is warranted

Looking to the Future: Key Points for Sustainable Management of Northern Great Plains Grasslands

The grasslands of the northern Great Plains (NGP) region of North America are considered endangered ecosystems and priority conservation areas yet have great ecological and economic importance. Grasslands in the NGP are no longer self-regulating adaptive systems. The challenges to these grasslands are widespread and serious (e.g. climate change, invasive species, fragmentation, altered disturbance regimes, and anthropogenic chemical loads). Because the challenges facing the region are dynamic, complex, and persistent, a paradigm shift in how we approach restoration and management of the grasslands in the NGP is imperative. The goal of this article is to highlight four key points for land managers and restoration practitioners to consider when planning management or restoration actions. First, we discuss the appropriateness of using historical fidelity as a restoration or management target because of changing climate, widespread pervasiveness of invasive species, the high level of fragmentation, and altered disturbance regimes. Second, we highlight ecosystem resilience and long-term population persistence as alternative targets. Third, because the NGP is so heavily impacted with anthropogenic chemical loading, we discuss the risks of ecological traps and extinction debt. Finally, we highlight the importance of using adaptive management and having patience during restoration and management. Consideration of these four points will help management and restoration of grasslands move toward a more successful and sustainable future. Although we specifically focus on the NGP of North America, these same issues and considerations apply to grasslands and many other ecosystems globally

CO-dependent H2 evolution by Rhodospirillum rubrum: Role of CODH:CooF complex

AbstractUpon exposure to CO during anaerobic growth, the purple phototrophic bacterium Rhodospirillum rubrum expresses a CO-oxidizing H2 evolving enzymatic system. The CO-oxidizing enzyme, carbon monoxide dehydrogenase (CODH), has been purified and extensively characterized. However the electron transfer pathway from CODH to the CO-induced hydrogenase that evolves H2 is not well understood. CooF is an Fe–S protein that is the proposed mediator of electron transfer between CODH and the CO-induced hydrogenase. Here we present the spectroscopic and biochemical properties of the CODH:CooF complex. The characteristic EPR signals observed for CODH are largely insensitive to CooF complexation. Metal analysis and EPR spectroscopy show that CooF contains 2 Fe4S4 clusters. The observation of 2 Fe4S4 clusters for CooF contradicts the prediction of 4 Fe4S4 clusters based on analysis of the amino acid sequence of CooF and structural studies of CooF homologs. Comparison of in vivo and in vitro CO-dependent H2 evolution indicates that ∼90% of the activity is lost upon cell lysis. We propose that the loss of two labile Fe–S clusters from CooF during cell lysis may be responsible for the low in vitro CO-dependent H2 evolution activity. During the course of these studies, a new assay for CODH:CooF was developed using membranes from an R. rubrum mutant that did not express CODH:CooF, but expressed high levels of the CO-induced hydrogenase. The assay revealed that the CO-induced hydrogenase requires the presence of CODH:CooF for optimal H2 evolution activity

Electronic Principles Governing the Stability and Reactivity of Ligated Metal and Silicon Encapsulated Transition Metal Clusters

A thorough understanding of the underlying electronic principles guiding the stability and reactivity of clusters has direct implications for the identification of stable clusters for incorporation into clusters-assembled materials with tunable properties. This work explores the electronic principles governing the stability and reactivity of two types of clusters: ligated metal clusters and silicon encapsulated transition metal clusters. In the first case, the reactivity of iodine-protected aluminum clusters, Al13Ix- (x=0-4) and Al14Iy- (y-0-5), with the protic species methanol was studied. The symmetrical ground states of Al13Ix- showed no reactivity with methanol but reactivity was achieved in a higher energy isomer of Al13I2- with iodines on adjacent aluminum atoms – complementary Lewis acid-base active sites were induced on the opposite side of the cluster capable of breaking the O-H bond in methanol. Al14Iy- (y=2-5) react with methanol, but only at the ligated adatom site. Reaction of methanol with Al14- and Al14I- showed that ligation of the adatom was necessary for the reaction to occur there – revealing the concept of a ligand-activated adatom. In the second case, the study focused heavily on CrSi12, a silicon encapsulated transition metal cluster whose stability and the reason for that stability has been debated heavily in the literature. Calculations of the energetic properties of CrSin (n=6-16) revealed both CrSi12 and CrSi14 to have enhanced stability relative to other clusters; however CrSi12 lacks all the traditional markers of a magic cluster. Molecular orbital analysis of each of these clusters showed the CNFEG model to be inadequate in describing their stability. Because the 3dz2 orbital of Cr is unfilled in CrSi12, this cluster has only 16 effective valence electrons, meaning that the 18-electron rule is not applicable. The moderate stability of CrSi12 can be accounted for by the crystal-field splitting of the 3d orbitals, which pushes the 3dz2 orbital up in energy. CrSi14, on the other hand, has 18 effective valence electrons on Cr, minimal 3d-orbital splitting, and does follow the 18-electron rule. A repetition of these calculations with WSin (n=6-16) showed similar results, except WSi12 shows all the markers of a magic cluster, due to the greater crystal-field splitting of 5d orbitals

Alcohol-Related Harms from Others' Drinking in India

Background: From 2005 to 2010, India faced a 19% increase in average adult per capita alcohol consumption. In a country where a large proportion of the population abstains from alcohol but heavy episodic consumption is common among those who drink, alcohol-related harms from others’ drinking may be substantial. Purpose: The purpose of this dissertation was to examine both the ethical issues raised in regards to harms from others drinking, and newly available epidemiological evidence about this in India. The main objectives were to: (1) apply a public health ethics framework to systematically consider the ethical implications of implementing policies to prevent alcohol-related harms to others; (2) understand the types of alcohol-related harms to children from adults’ drinking across domains of physical abuse, psychological abuse, and neglect; and (3) assess various types of tangible and intangible harm from strangers’ drinking and individuals’ characteristics that predict experiences of such harms. Methods: I examined public health ethics literature and generated evidence of harms from others’ drinking by analyzing cross-sectional data from household interviews administered in five Indian states in 2011-2012. Results: The compilation of data on harms from others’ drinking can strengthen the ethical justification for evidence-based alcohol control policies. Harms to children from adults’ drinking are a serious problem in India: 44% of respondents reported at least one alcohol-related harm to children in the past year. Sixteen percent of respondents reported physical alcohol-related harms to children. Strangers are also affected by others’ drinking: 63% of respondents experienced at least one tangible or intangible harm from strangers’ drinking, with nearly 48% of respondents experiencing tangible harm. Conclusions: Public health professionals have an obligation to consider the ethics associated with implementing alcohol control policies. The findings from this dissertation suggest that people with limited control over their exposure to another person’s drinking, including children and strangers, are burdened by others’ alcohol use. Interventions, such as increased use and enforcement of evidence-based alcohol control policies, are needed to prevent alcohol-related harms to children and strangers in India. Future research should use harms to others data for evaluating the effectiveness of alcohol policies

I am me : adolescent perspectives of a school-based universal intervention program designed to promote emotional competence

The aim of this paper is to describe a school-based universal intervention (the Tilly’s Life Center “I Am Me” program) to promote emotional competence and social-emotional skills in adolescents. We present results of a mixed-methods program evaluation conducted in public schools in Southern California. In Study 1, sixteen students (grades 10-12) participated in focus groups after twelve weeks of intervention. In Study 2, fifty-four students (grades 9-10) participated in either the universal intervention program (I Am Me) or a no-intervention comparison group for thirty-six weeks. We conducted focus groups with 50 adolescents in the I Am Me program and used quantitative methods to measure self-esteem and perceived stress at four time points for both groups in Study 2. Descriptive data suggested improvements in self-esteem and perceived stress among individuals participating in the I Am Me group. Thematic analysis of focus group data indicated that participants perceived improvement in key areas of emotional development, including: emotional competence (understanding, expressing, and regulating emotions), self-regulation, self-esteem, and social skills. Moreover, participants perceived the intervention as relevant and as having a positive lifelong impact on their development. Further research is needed to empirically validate these outcomes using a randomized experimental design.peer-reviewe

Problem-solving teletherapy for adults with visual impairment: A feasibility study to improve access and treatment

Introduction: Adults with visual impairment are at increased risk of developing depression and experiencing a decreased quality of life, as compared to vision intact adults. However, there are many barriers to accessing health problems for this population. Purpose: The purpose of the study is to explore the impact of a virtual group-based intervention utilizing strategies from motivational interviewing and cognitive-behavioral problem-solving therapy to improve attendance and treatment outcome for adults with visual impairment. Specifically, the study will focus on improving previously demonstrated low rates of attendance, as well as improving depression, quality of life, problem-solving skills; and reducing cognitive distortions. Hypotheses: H1: It is hypothesized that the virtual group treatment, based on problem-solving therapy, will lead to an increase in attendance for adults with visual impairment, as compared to similar in vivo intervention. H2: It is hypothesized that the intervention will result in improvement in problem-solving skills and quality of life for adults with visual impairment. H3: It is hypothesized that the virtual group-based intervention will reduce depressive symptoms and frequency of cognitive distortions in visually impaired adults. Proposed Methods: Participants will be recruited on a voluntary basis from a non-profit organization that provides services for adults with visual impairment and blindness in a large metropolitan city in the Northeastern United States. Attendance will be operationalized as the percent of sessions attended by participants. Problem-solving skills will be operationalized as scores on the Social Problem-Solving Inventory, Revised (SPSI-R). Quality of life is operationalized as scores on the Quality of Life Inventory (QOLI). Depression will be operationalized as scores on the Patient Health Questionnaire (PHQ-9). Cognitive distortions will be operationalized as total scores on the Inventory of Cognitive Distortions (ICD). Proposed Analyses: The study will be a single subject, multiple-baseline design observed across group participants. This feasibility study was designed to examine the effect of a PST intervention on individuals with visual impairment to increase attendance, problem-solving skills, and quality of life, and to decrease depression and cognitive distortions. Attendance from this group will be compared to a previous, brief PST pilot group to determine if the more accessible teletherapy platform will increase engagement/attendance in the current group. Implications: It is hoped that results from this study will inform how teletherapy can be used to reduce barriers to attending treatment for adults with visual impairment. Additionally, it is hoped that the study will inform clinical assessment and treatment for adults with visual impairment

Cutting and Shuffling a Line Segment: Mixing by Interval Exchange Transformations

We present a computational study of finite-time mixing of a line segment by cutting and shuffling. A family of one-dimensional interval exchange transformations is constructed as a model system in which to study these types of mixing processes. Illustrative examples of the mixing behaviors, including pathological cases that violate the assumptions of the known governing theorems and lead to poor mixing, are shown. Since the mathematical theory applies as the number of iterations of the map goes to infinity, we introduce practical measures of mixing (the percent unmixed and the number of intermaterial interfaces) that can be computed over given (finite) numbers of iterations. We find that good mixing can be achieved after a finite number of iterations of a one-dimensional cutting and shuffling map, even though such a map cannot be considered chaotic in the usual sense and/or it may not fulfill the conditions of the ergodic theorems for interval exchange transformations. Specifically, good shuffling can occur with only six or seven intervals of roughly the same length, as long as the rearrangement order is an irreducible permutation. This study has implications for a number of mixing processes in which discontinuities arise either by construction or due to the underlying physics.Comment: 21 pages, 10 figures, ws-ijbc class; accepted for publication in International Journal of Bifurcation and Chao