Colonization of malaria vectors under semi-field conditions as a strategy for maintaining genetic and phenotypic similarity with wild populations

Background Malaria still accounts for an estimated 207 million cases and 627,000 deaths worldwide each year. One proposed approach to complement existing malaria control methods is the release of genetically-modified (GM) and/or sterile male mosquitoes. As opposed to laboratory colonization, this requires realistic semi field systems to produce males that can compete for females in nature. This study investigated whether the establishment of a colony of the vector Anopheles arabiensis under more natural semi-field conditions can maintain higher levels of genetic diversity than achieved by laboratory colonization using traditional methods.<p></p> Methods Wild females of the African malaria vector An. arabiensis were collected from a village in southern Tanzania and used to establish new colonies under different conditions at the Ifakara Health Institute. Levels of genetic diversity and inbreeding were monitored in colonies of An. arabiensis that were simultaneously established in small cage colonies in the SFS and in a large semi-field (SFS) cage and compared with that observed in the original founder population. Phenotypic traits that determine their fitness (body size and energetic reserves) were measured at 10th generation and compared to founder wild population.<p></p> Results In contrast to small cage colonies, the SFS population of An. arabiensis exhibited a higher degree of similarity to the founding field population through time in several ways: (i) the SFS colony maintained a significantly higher level of genetic variation than small cage colonies, (ii) the SFS colony had a lower degree of inbreeding than small cage colonies, and (iii) the mean and range of mosquito body size in the SFS colony was closer to that of the founding wild population than that of small cage colonies. Small cage colonies had significantly lower lipids and higher glycogen abundances than SFS and wild population.<p></p> Conclusions Colonization of An. arabiensis under semi-field conditions was associated with the retention of a higher degree of genetic diversity, reduced inbreeding and greater phenotypic similarity to the founding wild population than observed in small cage colonies. Thus, mosquitoes from such semi-field populations are expected to provide more realistic representation of mosquito ecology and physiology than those from small cage colonies.<p></p&gt

Acute post-disaster medical needs of patients with diabetes: emergency department use in New York City by diabetic adults after Hurricane Sandy.

OBJECTIVE: To evaluate the acute impact of disasters on diabetic patients, we performed a geospatial analysis of emergency department (ED) use by New York City diabetic adults in the week after Hurricane Sandy. RESEARCH DESIGN AND METHODS: Using an all-payer claims database, we retrospectively analyzed the demographics, insurance status, and medical comorbidities of post-disaster ED patients with diabetes who lived in the most geographically vulnerable areas. We compared the patterns of ED use among diabetic adults in the first week after Hurricane Sandy\u27s landfall to utilization before the disaster in 2012. RESULTS: In the highest level evacuation zone in New York City, postdisaster increases in ED visits for a primary or secondary diagnosis of diabetes were attributable to a significantly higher proportion of Medicare patients. Emergency visits for a primary diagnosis of diabetes had an increased frequency of certain comorbidities, including hypertension, recent procedure, and chronic skin ulcers. Patients with a history of diabetes visited EDs in increased numbers after Hurricane Sandy for a primary diagnosis of myocardial infarction, prescription refills, drug dependence, dialysis, among other conditions. CONCLUSIONS: We found that diabetic adults aged 65 years and older are especially at risk for requiring postdisaster emergency care compared to other vulnerable populations. Our findings also suggest that there is a need to support diabetic adults particularly in the week after a disaster by ensuring access to medications, aftercare for patients who had a recent procedure, and optimize their cardiovascular health to reduce the risk of heart attacks

AMPA Receptor Phosphorylation and Synaptic Colocalization on Motor Neurons Drive Maladaptive Plasticity below Complete Spinal Cord Injury.

Clinical spinal cord injury (SCI) is accompanied by comorbid peripheral injury in 47% of patients. Human and animal modeling data have shown that painful peripheral injuries undermine long-term recovery of locomotion through unknown mechanisms. Peripheral nociceptive stimuli induce maladaptive synaptic plasticity in dorsal horn sensory systems through AMPA receptor (AMPAR) phosphorylation and trafficking to synapses. Here we test whether ventral horn motor neurons in rats demonstrate similar experience-dependent maladaptive plasticity below a complete SCI in vivo. Quantitative biochemistry demonstrated that intermittent nociceptive stimulation (INS) rapidly and selectively increases AMPAR subunit GluA1 serine 831 phosphorylation and localization to synapses in the injured spinal cord, while reducing synaptic GluA2. These changes predict motor dysfunction in the absence of cell death signaling, suggesting an opportunity for therapeutic reversal. Automated confocal time-course analysis of lumbar ventral horn motor neurons confirmed a time-dependent increase in synaptic GluA1 with concurrent decrease in synaptic GluA2. Optical fractionation of neuronal plasma membranes revealed GluA2 removal from extrasynaptic sites on motor neurons early after INS followed by removal from synapses 2 h later. As GluA2-lacking AMPARs are canonical calcium-permeable AMPARs (CP-AMPARs), their stimulus- and time-dependent insertion provides a therapeutic target for limiting calcium-dependent dynamic maladaptive plasticity after SCI. Confirming this, a selective CP-AMPAR antagonist protected against INS-induced maladaptive spinal plasticity, restoring adaptive motor responses on a sensorimotor spinal training task. These findings highlight the critical involvement of AMPARs in experience-dependent spinal cord plasticity after injury and provide a pharmacologically targetable synaptic mechanism by which early postinjury experience shapes motor plasticity

Application of the DRA method to the calculation of the four-loop QED-type tadpoles

We apply the DRA method to the calculation of the four-loop `QED-type' tadpoles. For arbitrary space-time dimensionality D the results have the form of multiple convergent sums. We use these results to obtain the epsilon-expansion of the integrals around D=3 and D=4.Comment: References added, some typos corrected. Results unchange

On Epsilon Expansions of Four-loop Non-planar Massless Propagator Diagrams

We evaluate three typical four-loop non-planar massless propagator diagrams in a Taylor expansion in dimensional regularization parameter $\epsilon=(4-d)/2$ up to transcendentality weight twelve, using a recently developed method of one of the present coauthors (R.L.). We observe only multiple zeta values in our results.Comment: 3 pages, 1 figure, results unchanged, discussion improved, to appear in European Physical Journal

Analytic Results for Massless Three-Loop Form Factors

We evaluate, exactly in d, the master integrals contributing to massless three-loop QCD form factors. The calculation is based on a combination of a method recently suggested by one of the authors (R.L.) with other techniques: sector decomposition implemented in FIESTA, the method of Mellin--Barnes representation, and the PSLQ algorithm. Using our results for the master integrals we obtain analytical expressions for two missing constants in the ep-expansion of the two most complicated master integrals and present the form factors in a completely analytic form.Comment: minor revisions, to appear in JHE

Beluga whale (Delphinapterus leucas) acoustic foraging behavior and applications for long term monitoring

This paper is not subject to U.S. copyright. The definitive version was published in Castellote, M., Mooney, A., Andrews, R., Deruiter, S., Lee, W.-J., Ferguson, M., & Wade, P. Beluga whale (Delphinapterus leucas) acoustic foraging behavior and applications for long term monitoring. Plos One, 16(11), (2021): e0260485, https://doi.org/10.1371/journal.pone.0260485.Cook Inlet, Alaska, is home to an endangered and declining population of 279 belugas (Delphinapterus leucas). Recovery efforts highlight a paucity of basic ecological knowledge, impeding the correct assessment of threats and the development of recovery actions. In particular, information on diet and foraging habitat is very limited for this population. Passive acoustic monitoring has proven to be an efficient approach to monitor beluga distribution and seasonal occurrence. Identifying acoustic foraging behavior could help address the current gap in information on diet and foraging habitat. To address this conservation challenge, eight belugas from a comparative, healthy population in Bristol Bay, Alaska, were instrumented with a multi-sensor tag (DTAG), a satellite tag, and a stomach temperature transmitter in August 2014 and May 2016. DTAG deployments provided 129.6 hours of data including foraging and social behavioral states. A total of 68 echolocation click trains ending in terminal buzzes were identified during successful prey chasing and capture, as well as during social interactions. Of these, 37 click trains were successfully processed to measure inter-click intervals (ICI) and ICI trend in their buzzing section. Terminal buzzes with short ICI (minimum ICI <8.98 ms) and consistently decreasing ICI trend (ICI increment range <1.49 ms) were exclusively associated with feeding behavior. This dual metric was applied to acoustic data from one acoustic mooring within the Cook Inlet beluga critical habitat as an example of the application of detecting feeding in long-term passive acoustic monitoring data. This approach allowed description of the relationship between beluga presence, feeding occurrence, and the timing of spawning runs by different species of anadromous fish. Results reflected a clear preference for the Susitna River delta during eulachon (Thaleichthys pacificus), Chinook (Oncorhynchus tshawytscha), pink (Oncorhynchus gorbuscha), and coho (Oncorhynchus kisutch) salmon spawning run periods, with increased feeding occurrence at the peak of the Chinook and pink salmon runs.Project funding was provided by Georgia Aquarium, the Marine Mammal Laboratory of the Alaska Fisheries Science Center (MML/AFSC). Tagging was funded by the NOAA Fisheries Office of Science and Technology’s Ocean Acoustics Program. DTAG data analysis was funded by the U.S. Marine Mammal Commission grant #16-239. Funding for collecting and analyzing Cook Inlet beluga acoustic data in Susitna Delta was provided by the National Marine Fisheries Service Section 6 Office to the Alaska Department of Fish and Game. This publication is partially funded by the Cooperative Institute for Climate, Ocean, and Ecosystem Studies (CICOES), University of Washington, under NOAA Cooperative Agreement NA15OAR4320063, Contribution No. 2021-1145

The cancer gene WWOX behaves as an inhibitor of SMAD3 transcriptional activity via direct binding

Background: The WW domain containing protein WWOX has been postulated to behave as a tumor suppressor in breast and other cancers. Expression of this protein is lost in over 70% of ER negative tumors. This prompted us to investigate the phenotypic and gene expression effects of loss of WWOX expression in breast cells. Methods: Gene expression microarrays and standard in vitro assays were performed on stably silenced WWOX (shRNA) normal breast cells. Bioinformatic analyses were used to identify gene networks and transcriptional regulators affected by WWOX silencing. Co-immunoprecipitations and GST-pulldowns were used to demonstrate a direct interaction between WWOX and SMAD3. Reporter assays, ChIP, confocal microscopy and in silico analyses were employed to determine the effect of WWOX silencing on TGFβ-signaling. Results: WWOX silencing affected cell proliferation, motility, attachment and deregulated expression of genes involved in cell cycle, motility and DNA damage. Interestingly, we detected an enrichment of targets activated by the SMAD3 transcription factor, including significant upregulation of ANGPTL4, FST, PTHLH and SERPINE1 transcripts. Importantly, we demonstrate that the WWOX protein physically interacts with SMAD3 via WW domain 1. Furthermore, WWOX expression dramatically decreases SMAD3 occupancy at the ANGPTL4 and SERPINE1 promoters and significantly quenches activation of a TGFβ responsive reporter. Additionally, WWOX expression leads to redistribution of SMAD3 from the nuclear to the cytoplasmic compartment. Since the TGFβ target ANGPTL4 plays a key role in lung metastasis development, we performed a meta-analysis of ANGPTL4 expression relative to WWOX in microarray datasets from breast carcinomas. We observed a significant inverse correlation between WWOX and ANGPTL4. Furthermore, the WWOXlo/ANGPTL4hi cluster of breast tumors is enriched in triple-negative and basal-like sub-types. Tumors with this gene expression signature could represent candidates for anti-TGFβ targeted therapies. Conclusions: We show for the first time that WWOX modulates SMAD3 signaling in breast cells via direct WW-domain mediated binding and potential cytoplasmic sequestration of SMAD3 protein. Since loss of WWOX expression increases with breast cancer progression and it behaves as an inhibitor of SMAD3 transcriptional activity these observations may help explain, at least in part, the paradoxical pro-tumorigenic effects of TGFβ signaling in advanced breast cancer.Fil: Ferguson, Brent W.. University of Texas; Estados UnidosFil: Gao, Xinsheng. University of Texas; Estados UnidosFil: Zelazowski, Maciej J.. University of Texas; Estados UnidosFil: Lee, Jaeho. University of Texas; Estados UnidosFil: Jeter, Collene R.. University of Texas; Estados UnidosFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Inmunológicas Básicas y Aplicadas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aldaz, Claudio Marcelo. University of Texas; Estados Unido

Modelflow Estimates of Stroke Volume Do Not Correlate With Doppler Ultrasound Estimates During Upright Posture

Orthostatic intolerance affects 6080% of astronauts returning from longduration missions, representing a significant risk to completing missioncritical tasks. While likely multifactorial, a reduction in stroke volume (SV) represents one factor contributing to orthostatic intolerance during stand and head up tilt (HUT) tests. Current measures of SV during stand or HUT tests use Doppler ultrasound and require a trained operator and specialized equipment, restricting its use in the field. BeatScope (Finapres Medical Systems BV, The Netherlands) uses a modelflow algorithm to estimate SV from continuous blood pressure waveforms in supine subjects; however, evidence supporting the use of Modelflow to estimate SV in subjects completing stand or HUT tests remain scarce. Furthermore, because the blood pressure device is held extended at heart level during HUT tests, but allowed to rest at the side during stand tests, changes in the finger arterial pressure waveform resulting from arm positioning could alter modelflow estimated SV. The purpose of this project was to compare Doppler ultrasound and BeatScope estimations of SV to determine if BeatScope can be used during stand or HUT tests. Finger photoplethysmography was used to acquire arterial pressure waveforms corrected for hydrostatic fingertoheart height using the Finometer (FM) and Portapres (PP) arterial pressure devices in 10 subjects (5 men and 5 women) during a stand test while simultaneous estimates of SV were collected using Doppler ultrasound. Measures were made after 5 minutes of supine rest and while subjects stood for 5 minutes. Next, SV estimates were reacquired while each arm was independently raised to heart level, a position similar to tilt testing. Supine SV estimates were not significantly different between all three devices (FM: 68+/-20, PP: 71+/-21, US: 73+/-21 ml/beat). Upon standing, the change in SV estimated by FM (18+/-8 ml) was not different from PP (21+/-12), but both were significantly less than US (37+/-16 ml, p<.05). Raising finger BP devices to heart level caused no significant change in SV measured with any of the devices (FM: 1.5+/-19, PP: 1.7+/-26, US: 0.5+/-6), although variability was 36x greater as assessed by both blood pressure devices compared to US. Retrospective analysis of blood pressure data to assess SV in 11 supine subjects revealed significantly different estimates between methods (FM: 95+/-17, US: 75+/-32, p<.05), but the change in SV resulting from HUT was similar between methods (FM: 37+/-9, US: 40+/-18 ml). However, the correlation coefficient determined from pairs of SV estimated by US and FM was weak (r2=0.03). These data suggest Modelflow cannot be used in lieu of Doppler ultrasound to estimate SV during stand or HUT tests. Further investigation should focus on identifying factors contributing to differences between these measurement techniques in order to make use of a simple method for assessing beatbybeat changes in SV during postural changes, especially during field testing

Keck/LRIS Spectroscopic Confirmation of Coma Cluster Dwarf Galaxy Membership Assignments

Keck/LRIS multi-object spectroscopy has been carried out on 140 of some of the lowest and highest surface brightness faint (19 < R < 22) dwarf galaxy candidates in the core region of the Coma Cluster. These spectra are used to measure redshifts and establish membership for these faint dwarf populations. The primary goal of the low surface brightness sample is to test our ability to use morphological and surface brightness criteria to distinguish between Coma Cluster members and background galaxies using high resolution HST/ACS images. Candidates were rated as expected members, uncertain, or expected background. From 93 spectra, 51 dwarf galaxy members and 20 background galaxies are identified. Our morphological membership estimation success rate is ~100% for objects expected to be members and better than ~90% for galaxies expected to be in the background. We confirm that low surface brightness is a very good indicator of cluster membership. High surface brightness galaxies are almost always background with confusion arising only from the cases of the rare compact elliptical galaxies. The more problematic cases occur at intermediate surface brightness. Many of these galaxies are given uncertain membership ratings, and these were found to be members about half of the time. Including color information will improve membership determination but will fail for some of the same objects that are already mis-identified when using only surface brightness and morphology criteria. Compact elliptical galaxies with B-V colors ~0.2 magnitudes redward of the red sequence in particular require spectroscopic follow-up. In a sample of 47 high surface brightness, UCD candidates, 19 objects have redshifts which place them in the Coma Cluster. Redshift measurements are presented and the use of indirect means for establishing cluster membership is discussed.Comment: Accepted for publication in ApJ, 25 pages, 15 figure