Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Modeling of c2h2 Zinc Finger Mutation of Putative Human Transcription Factor SALL4

Motivation. The SALL4 gene, Drosophila’s region specific homeotic sal (spalt)–like gene family member, encodes for a zinc finger (ZF) transcription factor (TF). Mutations of the SALL4 have been demonstrated to cause the Okihiro syndrome a combination of Duane retraction syndrome and radial ray defects. We have studied a missense point mutation of the SALL4 (nucleotide substitution 2663A�: G, residues substitution His:888�: Arg:888) positioned within the first c2h2 ZF of the C–terminal double ZF motif in the SALL4 gene identified in an Italian three–generation family, some members of which displayed the clinical features of the Okihiro syndrome. We performed a molecular modeling study on the wild type (wt) and mutated (mt) ZF domains of the SALL4 TF with the goal to propose a plausible hypothesis relating the modeled structural and energetic differences between the wt and mt forms to the defects connected with the observed mutation. Method. Sequence alignment, homology protein modeling and molecular mechanics using CFF91 force field were utilized to build and refine the ZF models and to estimate their stability and DNA–binding affinity. Results. We have modeled wt and mt ZF motifs of the SALL4 TF based on sequence homology with ZF domains of TFs with known crystal structures co–crystallized with a B–DNA segment. Secondary structure, zinc ion binding and DNA binding of the two static ZF models were analyzed in terms of mutual r.m.s. deviations and intramolecular and intermolecular interaction energies. Conclusions. The modeled wt and mt forms of ZF motif of the SALL4 TF did not display significant structural differences cased by steric strain or charge of the bulkier Arg:888 and retained similar supersecondary structures and comparable strength of the zinc ion binding. However, more significant differences were predicted in their binding affinities to DNA. Calculated higher DNA binding affinity (and possibly also changed specificity) of the mt form of the ZF could be the reason for the altered activator/repressor function of the mutant form of the SALL4 TF at its natural target gene or the cause for erroneous targeting of a different DNA sequence of the same or another gene. We may thus hypothesize that the pathogenic effects of the mutation could be related to the altered regulation function by making the dissociation of the mt SALL4 TF–gene adducts more difficult.
The Effects of Cinnamomum cassia Blume, Aconitum carmichaeli Debx, and Pueraria lobata Benth on Glucose and Energy Metabolism in C2C12 Myotubes

Objectives: The prevalence of obesity and metabolic syndrome is increasing worldwide. Regulation of cellular energy metabolis has the potential to be manipulated therapeutically to serve as a target for obesity and insulin resistance. Skeletal muscle is regarded as a target for regulation of energy metabolism and insulin resistance. In this study, the authors investigated the regulatory effect of (Cinnamomum cassia Blume, CCB), Aconitum carmichaeli Debx (ACD), and Benth (Pueraria lobata Benth, PLB) on energy and glucose metabolism in C2C12 myotubes. Methods: The water extracts of CCB, ACD, and PLB (0.5 mg/ml) were treated in differentiated C2C12 myotubes. The expressions of adenosine monophosphate-activated protein kinase (AMPK) and phosphorylation AMPK were detected with western blotting. Glucose metabolism was investigated with glucose uptake assay and glucose consumption assay, total adenosine triphosphate (ATP) content was also analyzed. Results: CCB, ACD, and PLB activated the phophorylation of AMPK, they also increased the glucose metabolism and total ATP contents in C2C12 myotubes. Conclusions: This study suggests that CCB, ACD, and PLB have the potential to increase energy and glucose metabolism in skeletal muscle.
Weather conditions and variation in timing of spring and fall migrations of migratory caribou

Species that make long-distance migrations face changes in the phenology of natural processes linked to global climate changes. Mismatch between the onset of resources and arrival on breeding grounds or changes in the conditions faced during migration such as early snowmelt in northern environments could have severe impacts on migrant populations. We investigated the impact of local weather and broad-scale climate and of the availability of forage resources on timing of spring and fall migrations of migratory caribou (Rangifer tarandus) from the Rivière-George and Rivière-aux-Feuilles herds in northern Québec and Labrador, Canada. We tested the effect of local weather using data provided by the Canadian Regional Climate Model, a large-scale climate index, snow and ice cover, and the Normalized Difference Vegetation Index on departure and arrival dates of 377 spring migrations and 499 fall migrations of female caribou. Since 2000, except for the spring arrival, migrations tended to occur earlier. Spring arrival was delayed when caribou encountered mild temperatures and abundant precipitation during migration, as early snowmelt may increase cost of movements. At greater population sizes, caribou seemed to limit the time spent on summer range by arriving later and departing earlier, possibly to limit competition for summer forage. During fall, caribou adjusted their migration to conditions en route because they arrived earlier if November was snowy and mild, possibly to limit the costs of moving through deep snow. Like numerous migrant species, most caribou herds are declining, and it is crucial to assess which environmental factors affect migrant populations. Our study contributes to the understanding of the impact of local weather conditions and climate change on migratory land mammals.
Evaluation of Angiogenesis Inhibitors Using the HUVEC Fibrin Bead Sprouting Assay

[Abstract] Angiogenesis, the growth of new blood vessels from pre-existing vessels, is a critical process that occurs during normal development and tumor formation. Targeting tumor angiogenesis by blocking the activity of vascular endothelial growth factor (VEGF) has demonstrated some clinical benefit; nevertheless there is a great need to target additional angiogenic pathways. We have found that the human umbilical vein endothelial cell (HUVEC) fibrin bead sprouting assay (FBA) is a robust and predictive in vitro assay to evaluate the activity of angiogenesis inhibitors. Here, we describe an optimized FBA protocol for the assessment of biological inhibitors of angiogenesis and the automated quantification of key endpoints.
Molecular mechanisms specifying Satb2/Ctip2-positive neurons in layer V of mouse somatosensory cortex and characterization of their morphology, connectivity, molecular profile and electrophysiological properties

The mammalian cerebral cortex is subdivided into several tangential domains calledfunctional areas, deputed to the elaboration of motor and sensory inputs and implementation of motor plans. Each functional area is constituted by six layers of projection neurons with different morphologies, connectivity and molecular codes.Several transcription factors specifying different subclasses of neurons have been identified so far. Fezf2 and Ctip2 promote the specification of subcerebralPNs, whereas Satb2 promotes callosal identity, mainly by repressing Ctip2transcription through the recruitment of the NURD complex to the Ctip2 locus.However, little is known about the mechanisms specifying their features in a timeandareal-Specific manner. In this study I show that a population of cells co-Expressing molecular markers of CPN and SCPN neurons, Satb2 and Ctip2, becomes first specified in layers V and VI of rostro-Medial mouse neocortex at perinatal stages and progressively increases between P0 and P21 in somatosensory areas. I found that in neocortices lacking COUP-TFI, a transcription factor involved in arealization, the number of Satb2/Ctip2 co-Expressing cells increases abnormally in layer V of the prospective somatosensory area. I demonstrated that LMO4 ectopic and premature expression of LMO4 in COUP-TFI mutant transgenic line derepresses Ctip2 in Satb2 positive cells by disturbing the assembly of the NURD complex at Ctip2 locus. Moreover, by the use of a transgenic line expressing GFP in layer V neurons and of vital dyes, I analysed morphology, connectivity and electrophysiological activity of this hybrid class of neurons.development. Toget
Genetic Differentiation in Moroccan Opuntia ficus-indica Cultivars Using Simple Sequence Repeat (SSR) Markers

Estimation of genetic parameters at SSR loci can be applied for assessing the differences between cultivars or populations, either for variety distinction or the management of genetic resources. In this study, 13 Opuntia ficus-indica cultivars were analyzed using 10 SSR markers selected for studying the genetic diversity among these chosen cultivars. Over the 10 SSR markers, a total of 45 reproducible bands were scored with an average of 4.5 alleles/locus, while the observed heterozygosity (Ho) values of amplified loci ranged from 0.15 (SSR1) to 0.92 (SSR2 and SSR 11). Genetic distance analysis of the 13 cultivars showed a large genetic differentiation (GST = 0.47) and high number of different groups. Most of the accessions were not found to be clustered according to their eco-geographical origin. In addition, each cultivar was characterized by its own multiallelic combination between loci. The results revealed the usefulness of SSR in understanding of genetic diversity in Moroccans Barbary fig cultivars, thus being helpful to set up rational decisions concerning the establishment of a national reference collection.
Quality of meat and fat from three breeding lines of chickens served feed with or without antibiotic growth stimulator.

SummaryThe aim of the study was to compare the breeding efficaciousness of chicken broilers, physicochemical andsensory quality of meat and composition of fatty acids of fat from three breeding lines of chicken served feedwith or without growth stimulator (control group). It was found that adding an antibiotic growth stimulatorincreased the production efficiency of Hubbard and ISA 215 lines. Free-range chickens, certified I 957, scoredthe lowest production effects (in both feeding groups) when compared to the remaining breeding groups, butat the same time were healthier and there was a lower percentage of death rate amongst these birds. Thebreast muscles of Hubbard line chickens where antibiotics were contained in their feed were found to havesignificantly more protein and less fat than the control group. Additionally, breast muscles displayed the besttechnological properties in both feeding groups independent of stimulator addition. The sensory quality ofmeat was not influenced by the breeding line or addition of antibiotics. Intramuscular fat from chickens fedwith the addition of growth stimulator contained a slightly lower amount of saturated and monounsaturatedfatty acids, but at the same time a higher amount of polyunsaturated fatty acids. The oxidation rate wasfastest in the abdominal fat from the Hubbard line fed with the addition of antibiotics. This was probably dueto a higher content of polyunsaturated and lower monounsaturated fatty acid content as mentioned above.Keywords: chicken broilers, meat quality
Relay intercropping and mineral fertilizer effects on biomass production, maize productivity and weed dynamics in contrasting soils under conservation agriculture

SUMMARY Cash-constrained farmers who cannot afford herbicides and mineral fertilizers may incorporate green manure cover crops (GMCCs) as relay crops to aid in management of weeds and nitrogen in maize systems under conservation agriculture in cases where rotations are a challenge. An experiment was conducted at two sites with contrasting soil types, University of Zimbabwe farm (clay) and Domboshawa Training Centre (sandy) to investigate the effects of maize/velvet bean intercropping at 8 weeks after planting maize (WAPM), applying different fertilizer rates and exploring their interactive effects on weed composition, maize productivity and biomass production [total maize non-cob biomass (stover) plus GMCC biomass]. The performance of the system depended largely on the amount of rainfall received within and across the seasons, sites and their interaction; also on the amount of fertilizer applied. Generally, biomass yields attained by velvet bean [Mucuna pruriens L. (DC.)] were lower than reported previously. Maize grain yield and weed diversity were higher in treatments with higher fertilizer rates, reaching up to 5·1 t/ha and 1·39, respectively. Generally, the highest weed diversity and highest maize grain yield values were observed in maize/velvet bean combinations and higher fertilizer rates (i.e. 0·27 and 4·8 t/ha, respectively) in the sandy soil. Higher fertilizer rates resulted in greater maize stover yield and this contributed greatly to the biomass productivity of the system in the sandy soil in the 2012/13 season, while the high biomass productivity observed in velvet bean in the clay site in the final season contributed significantly to productivity. Maize productivity was not affected by velvet bean introduced at 8 WAPM in any of the seasons. The present study showed that relay cropping velvet bean as late as 8 WAPM and onwards has potential to increase biomass production without compromising maize yields. However, planting it as late as 8 WAPM results in reduced productivity due to reduced moisture availability.
0868 Regulation of sterol regulatory element binding protein-1 in bovine mammary epithelial cells

The key transcription factor sterol regulatory element binding protein-1 (SREBP1) plays a central role in milk fat synthesis. SREBP1 stimulates the transcription of genes encoding lipogenic enzymes. The overall objective of these studies was to investigate the mechanisms of SREBP1 regulation by nutrients. In the first study, chromatin immunoprecipitation (ChIP) accompanied with deep-sequencing was employed to investigate the potential sterol regulatory elements (SRE) in the promoter of SREBP1target genes. The SRE in three known SREBP1-target genes SREBP1, fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD) were first validated in a bovine mammary epithelial cell line (MacT) and in bovine mammary tissues. At least one or two SRE binding sites in 24 selected lipogenic genes were identified within 50,000 base pair to the 5’-transcription start site through ChIP-seq. The genes closest to the highest enriched peaks were involved in cell integrity, defense or signal transduction whereas lipogenic genes were not among the top enrichment leading to the questions about the success of the ChIP. The second study was conducted to determine the effect of t10, c12-conjugated linoleic acid (CLA) on insulin induced gene-1 (Insig1), an endoplasmic reticulum (ER) protein that anchors SREBP1 and prevents proteolytic activation of SREBP1. MacT cells were treated with increasing levels of t10, c12-CLA. High concentration of t10, c12-CLA inhibited Insig1 degradation therefore decreased SREBP1 maturation. Furthermore, immunoprecipitation (IP) confirmed that t10, c12-CLA reduced Insig1 proteasomal
Investigating the Intrinsic and Extrinsic Drivers of Primate Heterothermy

Investigating the Intrinsic and Extrinsic Drivers of Primate Heterothermy by Sheena Lee Faherty Department of Biology Duke University Date:_______________________ Approved: ___________________________ Anne D. Yoder, Supervisor ___________________________ Manuel Leal ___________________________ Sandra L. Martin ___________________________ Kathleen K. Smith ___________________________ Gregory A. Wray An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biology in the Graduate School of Duke University 2016 Copyright by Sheena Lee Faherty 2016
Busulfan Selectively Induces Cellular Senescence Via a p53-Independent but Erk-p38 MAPK-Dependent Mechanism.

Busulfan (BU), an alkylating agent, has been used extensively for the depletion of leukemia cells and normal hematopoietic stem cells (HSCs) prior to bone marrow transplantation. However, its mechanism(s) of action is unknown. Our laboratory has previously shown that BU primarily depletes HSCs by induction of senescence, but not apoptosis. In the present study, we investigated the molecular mechanisms whereby BU induces cellular senescence utilizing WI38 human diploid fibroblasts as a model system. We found that WI38 fibroblasts incubated with BU (from 7.5 to 120μM) for 24 h underwent senescence but not apoptosis in a dose-independent manner, whereas cells incubated with 80μM and 20μM etoposide (Etop) committed to apoptosis and senescence, respectively. The induction of WI38 cell senescence by Etop was associated with p53 activation and could be attenuated by down-regulation of p53 using a-PFT or p53 siRNA. In contrast, WI38 cell senescence induced by BU was associated with prolonged activation of Erk, p38 and JNK, and could be suppressed by the inhibition of Erk and p38 MAPKs with PD98059 and SB203580, respectively. Upon release from Erk and p38 inhibition, BU-treated cells proceeded to DNA synthesis and cell division. However, inhibition of p53 with a-PFT or p53 siRNA, or JNK with SP600125, failed to protect WI38 cells from BU-induced senescence. These findings suggest that BU is a distinctive chemotherapeutic agent that can selectively induce cellular senescence through the Erk and p38 MAPK pathways.
CYTO-EMBRYOLOGICAL STUDIES OF SEA URCHINS. II. BLASTULA STAGE

1. The accumulation of a fluid under the hyaline plasma layer of Strongylocentrotus pulcherrimus eggs, and its movement during cleavage and interkinesis are described. It is shown that an increase in volume takes place in connection with each cleavage, and that the accumulated fluid comes around to the center of the larva, giving rise to the segmentation cavity. 2. Gum arabic prevents the fluid accumulation during early cleavage periods and reduces the volume of the segmentation cavity in later stages. Raising the Ca level of the medium brings about a similar result, by causing a hardening of the hyaline plasma layer and thus preventing increase in size. 3. Moore's finding—hat at the time of hatching, the blastular wall, which has been permeable to cane sugar molecules, suddenly becomes impermeable to them—is confirmed. 4. After the migration of the primary mesenchyme cells from the blastular wall into the blastocoel, the vegetal hyaline layer which has been in contact with these cells is lifted up as fol.
Assessing data quality in citizen science (preprint)

Ecological and environmental citizen science projects have enormous potential to advance science, influence policy, and guide resource management by producing datasets that are otherwise infeasible to generate. This potential can only be realized, though, if the datasets are of high quality. While scientists are often skeptical of the ability of unpaid volunteers to produce accurate datasets, a growing body of publications clearly shows that diverse types of citizen science projects can produce data with accuracy equal to or surpassing that of professionals. Successful projects rely on a suite of methods to boost data accuracy and account for bias, including iterative project development, volunteer training and testing, expert validation, replication across volunteers, and statistical modeling of systematic error. Each citizen science dataset should therefore be judged individually, according to project design and application, rather than assumed to be substandard simply because volunteers generated it.
Development tendency of agricultural water structure in China.

Agricultural water structure (AWS) influences the efficiency and potential benefits of water use. The evolution history of AWS in China was analyzed in this study using agricultural water consumption data in China for 1949~2006. Agricultural water use level for 1949~2050 was divided into four periods of primary use, low efficiency use, reasonable use and high efficiency use in accordance with the evolution history and tendency of future AWS. The analysis shows that AWS in China is improving as the proportion of agricultural water consumption to total water use is steadily decreasing. The level of water use is increasingly harmonized among agriculture, forestry, herding and fishing as well as water consumption by grain crops, cash crops and grazing grass. The concept of economic agricultural water consumption is advanced, emphasizing water-saving via optimized AWS. A case study of North China illustrates that AWS optimization increases water use benefits and saves 199.94×108 m3 water per year. Integrative water-saving measures along with optimized AWS saves an additional 29.97×108 m3 water per year over water-saving measures alone.
Acidulated Sunflower Soapstock as an Energy Source in the Diet of Broiler Chickens

Acidulated soapstock is a by-product of the vegetable oil refining process and is rich in polyunsaturated fatty acids. The present study was conducted to evaluate the effect of dietary incorporation of acidulated sunflower soapstock (ASS) in broiler chicken diet as an energy source on their performance, carcass characteristics, and quality and immune response. A corn-soybean basal starter (0–3 wk, 2900 kcal ME/kg and 22% CP) and finisher (4–6 wk, 3000 kcal ME/kg and 20% CP) diet was prepared using sunflower oil (SFO) as an energy source (Control group). Subsequently 3 experimental diets were prepared by replacing SFO with ASS at 25, 50 and 100% level. Each diet was fed ad libitum at random to10 replicates of 5 chicks in each throughout the experimental period (0–6 wk) reared in stainless steel battery brooders under uniform management conditions. Dietary incorporation of ASS replacing SFO at either partially or completely had no adverse effect on body weight gain, feed conversion ratio, carcass characteristics (relative weight of dressed yield, liver, giblet and abdominal fat), relative weight of immune organs (bursa and spleen) and humoral immune response (antibody titres against sheep RBC) of broiler chickens. The protein and fat contents of breast and thigh meat of broilers were also not influenced by the incorporation of ASS in the diets. The TBARS (mg malondialdehyde/g tissue) concentration in the breast meat was not affected, however, TBARS concentration was significantly (P<0.05) increased in thigh meat in the diet in which SFO was completely replaced by ASS. It is concluded that acidulated sunflower soapstock can be used as an energy source in the diet of broiler chickens.
Host Specificity in Microbe-Insect Interactions Insect control by bacterial, fungal, and viral pathogens

Among the alternatives for chemical insecticides are many pathogens that cause diseases in insects. These pathogens typically have a much narrower spectrum of activity than do chemicals, and thus they have excellent promise for use as selective biological control agents for insect pests. Only one insect pathogen, the bacterium Bacillus thuringiensis (Bt), is used with any frequency at present in the United States. However, the use of others, including certain viruses, fungi, and protozoa, is expected to increase as the use of chemicals declines. The prospect of using pathogens more widely as biological control agents is leading to greater scrutiny of their host specificity. Our current