High affinity inhibitors of the dopamine transporter (DAT): novel biotinylated ligands for conjugation to quantum dots

Compounds capable of inhibiting the dopamine transporter protein (DAT) that can be conjugated to cadmium selenide/zinc sulfide/core shell nanocrystals may be used to image the location and distribution of the DAT in neuronal cell membranes. This letter describes the synthesis of biotinylated analogs of the DAT antagonists GBR 12909 and GBR 12935 that can be attached to streptavidin coated cadmium selenide/zinc sulfide/core shell nanocrystals.     

Escherichia coli aceE variants coding pyruvate dehydrogenase improve the generation of pyruvate‐derived acetoin

Several chromosomally expressed AceE variants were constructed in Escherichia coli ΔldhA ΔpoxB ΔppsA and compared using glucose as the sole carbon source. These variants were examined in shake flask cultures for growth rate, pyruvate accumulation, and acetoin production via heterologous expression of the budA and budB genes from Enterobacter cloacae ssp. dissolvens. The best acetoin‐producing strains were subsequently studied in controlled batch culture at the one‐liter scale. PDH variant strains attained up to four‐fold greater acetoin than the strain expressing the wild‐type PDH. In a repeated batch process, the H106V PDH variant strain attained over 43 g/L of pyruvate‐derived products, acetoin (38.5 g/L) and 2R,3R‐butanediol (5.0 g/L), corresponding to an effective concentration of 59 g/L considering the dilution. The acetoin yield from glucose was 0.29 g/g with a volumetric productivity of 0.9 g/L·h (0.34 g/g and 1.0 g/L·h total products). The results demonstrate a new tool in pathway engineering, the modification of a key metabolic enzyme to improve the formation of a product via a kinetically slow, introduced pathway. Direct modification of the pathway enzyme offers an alternative to promoter engineering in cases where the promoter is involved in a complex regulatory network.     

Parents exposed to warming produce offspring lower in weight and condition

The parental environment can alter offspring phenotypes via the transfer of non‐genetic information. Parental effects may be viewed as an extension of (within‐generation) phenotypic plasticity. Smaller size, poorer physical condition, and skewed sex ratios are common responses of organisms to global warming, yet whether parental effects alleviate, exacerbate, or have no impact on these responses has not been widely tested. Further, the relative non‐genetic influence of mothers and fathers and ontogenetic timing of parental exposure to warming on offspring phenotypes is poorly understood. Here, we tested how maternal, paternal, and biparental exposure of a coral reef fish (Acanthochromis polyacanthus) to elevated temperature (+1.5°C) at different ontogenetic stages (development vs reproduction) influences offspring length, weight, condition, and sex. Fish were reared across two generations in present‐day and projected ocean warming in a full factorial design. As expected, offspring of parents exposed to present‐day control temperature that were reared in warmer water were shorter than their siblings reared in control temperature; however, within‐generation plasticity allowed maintenance of weight, resulting in a higher body condition. Parental exposure to warming, irrespective of ontogenetic timing and sex, resulted in decreased weight and condition in all offspring rearing temperatures. By contrast, offspring sex ratios were not strongly influenced by their rearing temperature or that of their parents. Together, our results reveal that phenotypic plasticity may help coral reef fishes maintain performance in a warm ocean within a generation, but could exacerbate the negative effects of warming between generations, regardless of when mothers and fathers are exposed to warming. Alternatively, the multigenerational impact on offspring weight and condition may be a necessary cost to adapt metabolism to increasing temperatures. This research highlights the importance of examining phenotypic plasticity within and between generations across a range of traits to accurately predict how organisms will respond to climate change.     

Focus: Vaccines: Myocarditis Following COVID-19 Vaccination: A Systematic Review of Case Reports

Introduction: COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), often presents with a spectrum of symptoms at varying levels of severity, ranging from asymptomatic patients to those with fatal complications, such as myocarditis. With increased availability of COVID-19 vaccines, the awareness of possible side effects has expanded as reports surface. This study reviewed cases of myocarditis following COVID-19 vaccination and with existing literature on COVID-19 infection-induced myocarditis to compare clinical courses and analyze possible mechanisms of action. Methods: A systematic review of literature was conducted to identify published case reports (as of February 3, 2022) pertaining to the development of myocarditis following COVID-19 vaccination with either Pfizer or Moderna for an in-depth analysis. Additional subgroup analyses were conducted based on age, past medical history, vaccine manufacturer, and dose number. Results: There were 53 eligible case reports that were included in this study. Patients were mostly male with a median age of 24 years, and the most reported symptom upon presentation was chest pain. Seventy percent of the cases involved the Pfizer vaccine with a majority of myocarditis developing subsequent to second dose. Resolution of symptoms was achieved in all but one patient. Clinical severity, as measured primarily by left ventricular ejection fraction, appeared to be worse among adult patients than pediatric, as well as for patients with comorbidities. Conclusion: This study revealed an observable association between COVID-19 vaccines and myocarditis. However, the clinical course and prognosis seem favorable and less prevalent than those conferred from natural infection.     

Up-regulation of the Cdc42 GTPase limits the replicative life span of budding yeast

Cdc42, a conserved Rho GTPase, plays a central role in polarity establishment in yeast and animals. Cell polarity is critical for asymmetric cell division, and asymmetric cell division underlies replicative aging of budding yeast. Yet how Cdc42 and other polarity factors impact life span is largely unknown. Here we show by live-cell imaging that the active Cdc42 level is sporadically elevated in wild type during repeated cell divisions but rarely in the long-lived bud8 deletion cells. We find a novel Bud8 localization with cytokinesis remnants, which also recruit Rga1, a Cdc42 GTPase activating protein. Genetic analyses and live-cell imaging suggest that Rga1 and Bud8 oppositely impact life span likely by modulating active Cdc42 levels. An rga1 mutant, which has a shorter life span, dies at the unbudded state with a defect in polarity establishment. Remarkably, Cdc42 accumulates in old cells, and its mild overexpression accelerates aging with frequent symmetric cell divisions, despite no harmful effects on young cells. Our findings implicate that the interplay among these positive and negative polarity factors limits the life span of budding yeast.     

Genetic differentiation and signatures of local adaptation revealed by RADseq for a highly dispersive mud crab Scylla olivacea (Herbst, 1796) in the Sulu Sea

Connectivity of marine populations is shaped by complex interactions between biological and physical processes across the seascape. The influence of environmental features on the genetic structure of populations has key implications for the dynamics and persistence of populations, and an understanding of spatial scales and patterns of connectivity is crucial for management and conservation. This study employed a seascape genomics approach combining larval dispersal modeling and population genomic analysis using single nucleotide polymorphisms (SNPs) obtained from RADseq to examine environmental factors influencing patterns of genetic structure and connectivity for a highly dispersive mud crab Scylla olivacea (Herbst, 1796) in the Sulu Sea. Dispersal simulations reveal widespread but asymmetric larval dispersal influenced by persistent southward and westward surface circulation features in the Sulu Sea. Despite potential for widespread dispersal across the Sulu Sea, significant genetic differentiation was detected among eight populations based on 1,655 SNPs (F_ST = 0.0057, p < .001) and a subset of 1,643 putatively neutral SNP markers (F_ST = 0.0042, p < .001). Oceanography influences genetic structure, with redundancy analysis (RDA) indicating significant contribution of asymmetric ocean currents to neutral genetic variation (Radj2 = 0.133, p = .035). Genetic structure may also reflect demographic factors, with divergent populations characterized by low effective population sizes (N _e < 50). Pronounced latitudinal genetic structure was recovered for loci putatively under selection (F_ST = 0.2390, p < .001), significantly correlated with sea surface temperature variabilities during peak spawning months for S. olivacea (Radj2 = 0.692–0.763; p < .050), suggesting putative signatures of selection and local adaptation to thermal clines. While oceanography and dispersal ability likely shape patterns of gene flow and genetic structure of S. olivacea across the Sulu Sea, the impacts of genetic drift and natural selection influenced by sea surface temperature also appear as likely drivers of population genetic structure. This study contributes to the growing body of literature documenting population genetic structure and local adaptation for highly dispersive marine species, and provides information useful for spatial management of the fishery resource.