Agricultural Policy, Migration, and Malaria in the 1930s United States

The Agricultural Adjustment Act (AAA) caused a population shift in the United States in the 1930s. Evaluating the effects of the AAA on the incidence of malaria can therefore offer important lessons regarding the broader consequences of demographic changes. Using a quasi-first difference model and a robust set of controls, we find a negative association between AAA expenditures and malaria death rates at the county level. Further, we find the AAA caused relatively low-income groups to migrate from counties with high-risk malaria ecologies. These results suggest that the AAA-induced migration played an important role in the reduction of malaria.

Evaluation of Fused Pyrrolothiazole Systems as Correctors of Mutant CFTR Protein

Cystic fibrosis (CF) is a genetic disease caused by mutations that impair the function of the CFTR chloride channel. The most frequent mutation, F508del, causes misfolding and premature degradation of CFTR protein. This defect can be overcome with pharmacological agents named "correctors". So far, at least three different classes of correctors have been identified based on the additive/synergistic effects that are obtained when compounds of different classes are combined together. The development of class 2 correctors has lagged behind that of compounds belonging to the other classes. It was shown that the efficacy of the prototypical class 2 corrector, the bithiazole corr-4a, could be improved by generating conformationally-locked bithiazoles. In the present study, we investigated the effect of tricyclic pyrrolothiazoles as analogues of constrained bithiazoles. Thirty-five compounds were tested using the functional assay based on the halide-sensitive yellow fluorescent protein (HS-YFP) that measured CFTR activity. One compound, having a six atom carbocyle central ring in the tricyclic pyrrolothiazole system and bearing a pivalamide group at the thiazole moiety and a 5-chloro-2-methoxyphenyl carboxamide at the pyrrole ring, significantly increased F508del-CFTR activity. This compound could lead to the synthesis of a novel class of CFTR correctors

Recurrence of the oxazole motif in tubulin colchicine site inhibitors with anti-tumor activity

Because of its wide spectrum of targets and biological activities, the oxazole ring is a valuable heterocyclic scaffold in the design of new therapeutic agents with anticancer, antiviral, antibacterial, anti-inflammatory, neuroprotective, antidiabetic and antidepressant properties. The presence of two heteroatoms, oxygen and nitrogen, offers possible interactions (hydrogen, hydrophobic, van der Waals or dipoles bonds) with a broad range of receptors and enzymes. Furthermore, the oxazole core conjugates low cytotoxicity with improved compound solubility and is well suited to structural modifications such as substitution with different groups and condensation to aromatic, heteroaromatic or non-aromatic rings, offering diversity when introduced into scaffolds. These features make it a very attractive nucleus in medicinal chemistry. Herein we present a diverse array of oxazole derivatives with potential therapeutic use in multiple tumor models. The emphasis has been addressed to compounds with anti-tubulin activity reported in literature in the last decade, describing their structural features, efficiency and future perspectives

GPCR Inhibition in Treating Lymphoma

G protein-coupled receptors (GPCRs) are important classes of cell surface receptors involved in multiple physiological functions. Aberrant expression, upregulation, and mutation of GPCR signaling pathways are frequent in many types of cancers, promoting hyperproliferation, angiogenesis, and metastasis. Recent studies showed that alterations of GPCRs are involved in different lymphoma types. Herein, we review the synthetic strategies to obtain GPCR inhibitors, focusing on CXCR4 inhibitors which represent most of the GPCR inhibitors available in the market or under preclinical investigations for these diseases

Seismotectonics of the active thrust front in southwestern Sicily: hints on the Belice and Selinunte seismogenic sources

We present a seismotectonic model of the active thrust front in western Sicily, which includes the area hit by the 1968 Belice earthquake sequence. The ~40 km long South-WEstern Sicilian Thrust (SWEST) is formed by two aligned albeit non-parallel fault arrays, the Granitola-Castelevetrano Thrust System (GCTS) in the west and the Partanna- Poggioreale Thrust System (PPTS) in the east. The ~NE-SW trending, NW-dipping GCTS straddles from the Pelagian coastline to Castelvetrano, is ~18 km long and composed of two segments, with the northern, ~12 km long one showing geodetic and geologic evidence of active deformation (Barreca et al., 2014). The segment is marked by a sharp gradient in Differential SAR interferometry (DinSAR and STAMPs) and GPS velocity fields. Geologic evidence include an up to 60 m high, and up to 15° steep scarp, which is the fore-limb of a broad fold involving Lower Pleistocene shore calcarenites, and cm-scale reverse displacement of an ancient road dated as early Bronze-Hellenistic age. Inversion of fault slip-lineation data from structures displacing the archaeological remains yields a ~N110°E shortening axis, consistent with the geodetic shortening direction estimated from GPS differential velocities. The ~ENE-WSW trending PPTS stretches from Partanna to the macro-seismic area of the 1968 earthquake sequence and is composed of two ~10 km long segments limited by relay ramps. Although geologic and geodetic evidence of deformation are less clear than for the GCTS, we nonetheless observe a gradient in interferometry data for the western segment, and evidence of slow deformation (creep?) in historical to recent (last ~400 yr?) man-made structures. Integration of geologic, geodetic and seismology data suggests the active folds and thrusts are the uppermost expression of steep (45°) crustal ramps (Monaco et al., 1996) which upthrust the Saccense platform at depth. Based on macroseismic and seismological evidence (Monaco et al., 1996), we contend that the PPTS was partly activated during the 1968 sequence, and that rupture stopped at the junction with the GCTS. The current geodetic strain accumulation on the GCTS, on the other hand, suggests that the fault array has been significantly loaded, and that its last important co-seismic event could have been caused the 4th–5th century A.D. destruction of Selinunte (Bottari et al., 2009)

Presence and biodistribution of perfluorooctanoic acid (PFOA) in Paracentrotus lividus highlight its potential application for environmental biomonitoring

The first determination of presence and biodistribution of PFOA in ninety specimens of sea urchin Paracentrotus lividus from two differently contaminated sites along Palermo’s coastline (Sicily) is reported. Analyses were performed on the sea urchins’ coelomic fluids, coelomocytes, gonads or mixed organs, as well as on seawater and Posidonia oceanica leaves samples from the collection sites. PFOA concentration ranged between 1 and 13 ng/L in seawater and between 0 and 794 ng/g in P. oceanica. The analyses carried out on individuals of P. lividus from the least polluted site (A) showed PFOA median values equal to 0 in all the matrices (coelomic fluid, coelomocytes and gonads). Conversely, individuals collected from the most polluted site (B) showed median PFOA concentrations of 21 ng/g in coelomic fluid, 153 ng/g in coelomocytes, and 195 ng/g in gonads. Calculated bioconcentration factors of log10BCF > 3.7 confirmed the very bioaccumulative nature of PFOA. Significant correlations were found between the PFOA concentration of the coelomic fluid versus the total PFOA concentration of the entire sea urchin. PERMANOVA (p = 0.001) end Welch's t-test (p < 0.001) analyses showed a difference between specimens collected from the two sites highlighting the potential application of P. lividus as sentinel species for PFOA biomonitoring

Geodetic and geological evidence of active tectonics in south-westernSicily (Italy)

Integrated geological, geodetic and marine geophysical data provide evidence of active deformation insouth-western Sicily, in an area spatially coincident with the macroseismic zone of the destructive 1968Belice earthquake sequence. Even though the sequence represents the strongest seismic event recordedin Western Sicily in historical times, focal solutions provided by different authors are inconclusive onpossible faulting mechanism, which ranges from thrusting to transpression, and the seismogenic sourceis still undefined. Interferometric (DInSAR) observations reveal a differential ground motion on a SW–NEalignment between Campobello di Mazara and Castelvetrano (CCA), located just west of the maximummacroseismic sector. In addition, new GPS campaign-mode data acquired across the CCA alignment doc-uments NW–SE contractional strain accumulation. Morphostructural analysis allowed to associate thealignment detected through geodetic measurements with a topographic offset of Pleistocene marine sed-iments. The on-land data were complemented by new high-resolution marine geophysical surveys, whichindicate recent contraction on the offshore extension of the CCA alignment. The discovery of archaeo-logical remains displaced by a thrust fault associated with the alignment provided the first likely surfaceevidence of coseismic and/or aseismic deformation related to a seismogenic source in the area. Resultsof the integrated study supports the contention that oblique thrusting and folding in response to NW–SEoriented contraction is still active. Although we are not able to associate the CCA alignment to the 1968seismic sequence or to the historical earthquakes that destroyed the ancient Greek city of Selinunte,located on the nearby coastline, our result must be incorporated in the seismic hazard evaluation of thisdensely populated area of Sicily

Propargyl carbamate-functionalized Cu(II)-metal organic framework after reaction with chloroauric acid: An x-ray photoelectron spectroscopy data record

A copper-containing metal organic framework was prepared using the new organic linker 5-(2-{[(prop-2-yn-1-yloxy)carbonyl]-amino} ethoxy)isophthalic acid [1,3-H2YBDC (where Y = alkYne and BDC = Benzene DiCarboxylate)] and functionalized with gold particles by reaction with HAuCl4 under thermal treatment in methanol. The resulting system was investigated by complementary techniques to obtain information on its structure and morphology. In the present work, x-ray photoelectron spectroscopy (XPS) was employed to analyze the chemical composition of a representative specimen. Besides wide scan spectra, data obtained by the analysis of the C 1s, O 1s, N 1s, Cu 2p, and Au 4f signals are presented and critically discussed. The results highlight the reduction of Au(III) to mostly Au(I) species. Overall, the data presented herein may act as useful guidelines for the eventual tailoring of material properties and their possible implementation toward functional applications in heterogeneous catalysis

Chedoke Arm and Hand Activity Inventory-9 (CAHAI-9): Perceived clinical utility within 14 days of stroke

Purpose: The Chedoke Arm and Hand Activity Inventory-9 (CAHAI-9) is an activity-based assessment developed to include relevant functional tasks and to be sensitive to clinically important changes in upper limb function. The aim of this study was to explore both therapists' and clients' views on the clinical utility of CAHAI-9 within 14 days of stroke. Method: Twenty-one occupational therapists actively working in stroke settings were recruited by convenience sampling from 8 hospitals and participated in semistructured focus groups. Five clients within 14 days of stroke were recruited by consecutive sampling from 1 metropolitan hospital and participated in structured individual interviews. The transcripts were analyzed thematically. Results: Six themes emerged from the focus groups and interviews: collecting information, decisions regarding client suitability, administration and scoring, organizational demands, raising awareness, and clients' perceptions of CAHAI-9 utility. All therapists agreed CAHAI-9 was suited for the stroke population and assisted identification of client abilities or difficulties within functional contexts. Opinions varied as to whether CAHAI-9 should be routinely administered with clients who had mild and severe upper limb deficits, but therapists agreed it was appropriate for clients with moderate deficits. Therapists made suggestions regarding refinement of the scoring and training to increase utility. All clients with stroke felt that the assessment provided reassurance regarding their recovery. Conclusion: The findings indicate that CAHAI-9 shows promise as an upper limb ability assessment for clients within 14 days of stroke

Botanical sources, chemistry, analysis, and biological activity of furanocoumarins of pharmaceutical interest

The aim of this work is to provide a critical review of plant furanocoumarins from different points of view, including their chemistry and biosynthetic pathways to their extraction, analysis, and synthesis, to the main biological activities found for these active compounds, in order to highlight their potential within pharmaceutical science. The limits and the possible improvements needed for research involving these molecules are also highlighted and discussed