Diversity in CO2 concentrating mechanisms among chemolithoautotrophs from genera Hydrogenovibrio, Thiomicrorhabdus, and Thiomicrospira, ubiquitous in sulfidic habitats worldwide

Members of Hydrogenovibrio, Thiomicrospira and Thiomicrorhabdus fix carbon at hydrothermal vents, coastal sediments, hypersaline lakes, and other sulfidic habitats. The genome sequences of these ubiquitous and prolific chemolithoautotrophs suggest a surprising diversity of mechanisms for dissolved inorganic carbon (DIC) uptake and fixation; these mechanisms are verified here. Carboxysomes are apparent in transmission electron micrographs of most of these organisms; lack of carboxysomes in Thiomicrorhabdus sp. Milos T2 and Tmr. arctica, and an inability to grow under low DIC conditions by Thiomicrorhabdus sp. Milos T2 are consistent with an absence of carboxysome loci in their genomes. For the remaining organisms, potential DIC transporters from four evolutionarily distinct families (Tcr0853/0854, Chr, SbtA, SulP) are located downstream of carboxysome loci. Transporter genes collocated with carboxysome loci, as well as some homologs located elsewhere on the chromosomes, had elevated transcript levels under low DIC conditions, as assayed by qRT-PCR. DIC uptake was measureable via silicone oil centrifugation when a representative of each of the four types of transporter was expressed in Escherichia coli. Expression of these genes in carbonic anhydrase-deficient E. coli EDCM636 enabled it to grow under low DIC conditions, consistent with DIC transport by these proteins. The results from this study expand the range of DIC transporters within the SbtA and SulP transporter families, verify DIC uptake by transporters encoded by Tcr_0853 and Tcr_0854 and their homologs, and introduce DIC as a potential substrate for transporters from the Chr family. IMPORTANCE Autotrophic organisms take up and fix DIC, introducing carbon into the biological component of the global carbon cycle. The mechanisms for DIC uptake and fixation by autotrophic Bacteria and Archaea are likely to be diverse, but have only been well-characterized among "Cyanobacteria". Based on genome sequences, members of Hydrogenovibrio, Thiomicrospira and Thiomicrorhabdus have a variety of mechanisms for DIC uptake and fixation. We verified that most of these organisms are capable of growing under low DIC conditions, when they upregulate carboxysome loci and transporter genes collocated with these loci on their chromosomes. When these genes, which fall into four evolutionarily independent families of transporters, are expressed in E. coli, DIC transport is detected. This expansion in known DIC transporters across four families, from organisms from a variety of environments, provides insight into the ecophysiology of autotrophs, as well as a toolkit for engineering microorganisms for carbon-neutral biochemistries of industrial importance

A dyadic approach to understanding the impact of breast cancer on relationships between partners during early survivorship

© 2016 The Author(s). Background: The shared impact of breast cancer for women and their male partners is emerging as an important consideration during the experience of a breast cancer diagnosis, particularly during survivorship. This study aimed to explore the experiences of women and their partners during early survivorship and contributes a range of insights into the lives of those intimately affected by breast cancer. Methods: In-depth interviews were completed with Australian women survivors of breast cancer (n = 8) and their partners (n = 8), between six months and five years following cessation of treatment. Questions included a focus on the women and their partners' daily experiences during early survivorship, including the management of ongoing symptoms, engagement in leisure and social interests, returning to work, communicating with each other, maintenance of the current relationship and other important roles and responsibilities. Thematic analysis was employed to determine key themes arising from the dyadic accounts of women and their partners' experiences during early breast cancer survivorship. Results: Women and their partners experienced many changes to their previous roles, responsibilities and relationships during early breast cancer survivorship. Couples also reported a range of communication, intimacy and sexuality concerns which greatly impacted their interactions with each other, adding further demands on the relationship. Three significant themes were determined: (1) a disconnection within the relationship - this was expressed as the woman survivor of breast cancer needing to prioritise her own needs, sometimes at the expense of her partner and the relationship; (2) reformulating the relationship - this reflects the strategies used by couples to negotiate changes within the relationship; and (3) support is needed to negotiate the future of the relationship - couples emphasised the need for additional support and resources to assist them in maintaining their relationship during early survivorship. Conclusion: It can be concluded that the early survivorship period represents a crucial time for both women and their partners and there are currently limited options available to meet their shared needs and preferences for support. Findings indicate that a suitable model of care underpinned by a biopsychosocial framework, access to comprehensive assessment, timely support and the provision of targeted resources are urgently needed to assist women and their partners during this critical time

Rogdi Defines GABAergic Control of a Wake-promoting Dopaminergic Pathway to Sustain Sleep in Drosophila

Kohlschutter-Tonz syndrome (KTS) is a rare genetic disorder with neurological dysfunctions including seizure and intellectual impairment. Mutations at the Rogdi locus have been linked to development of KTS, yet the underlying mechanisms remain elusive. Here we demonstrate that a Drosophila homolog of Rogdi acts as a novel sleep-promoting factor by supporting a specific subset of gamma-aminobutyric acid (GABA) transmission. Rogdi mutant flies displayed insomnia-like behaviors accompanied by sleep fragmentation and delay in sleep initiation. The sleep suppression phenotypes were rescued by sustaining GABAergic transmission primarily via metabotropic GABA receptors or by blocking wake-promoting dopaminergic pathways. Transgenic rescue further mapped GABAergic neurons as a cell-autonomous locus important for Rogdi-dependent sleep, implying metabotropic GABA transmission upstream of the dopaminergic inhibition of sleep. Consistently, an agonist specific to metabotropic but not ionotropic GABA receptors titrated the wake-promoting effects of dopaminergic neuron excitation. Taken together, these data provide the first genetic evidence that implicates Rogdi in sleep regulation via GABAergic control of dopaminergic signaling. Given the strong relevance of GABA to epilepsy, we propose that similar mechanisms might underlie the neural pathogenesis of Rogdi-associated KTS

The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up.

A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at alpha = 0.05 level (P-value \u3c0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for \u3c5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality

In Support of Industry-Conscious Disclosure Standards for Pharmaceutical and Biotechnology Patents

One of the fundamental requirements for a patent application is a disclosure of the invention via an accurate written description with sufficient detail to enable the recreation of the invention. The U.S. patent system has historically reviewed patent applications from various industries with a uniform set of requirements and standards. However, the biotechnology and pharmaceutical industries operate on notably extended product development timelines and face unique administrative pressures related to their products when compared with other industries. In response to these pressures, biotechnology and pharmaceutical companies have traditionally applied for patent protections through liberal use of genus claims and other strategies that allow for early and broad protection of groups of related products. However, three recent decisions by the Federal Circuit, and a subsequent appeal to the Supreme Court, have notably heightened patent disclosure requirements for technologies from these industries. This Comment discusses the Federal Circuit’s and Supreme Court’s decisions, compares these decisions to prior trends in the judiciary, and considers the potential impact of the decisions on the patent environment in the biotechnology and pharmaceutical industries. In light of the decisions’ potential impact on these industries, this Comment argues that the federal judiciary should align the disclosure standard more closely to the requirements of the Patent Act while protecting the usefulness of genus claims for the pharmaceutical and related industries

Effects of ultraviolet radiation on 25-hydroxyvitamin D3 synthesis in red-eared slider turtles (Trachemys scripta elegans)

OBJECTIVE: To determine whether there are increased concentrations of 25-hydroxyvitaminn D(3) in red-eared slider turtles (Trachemys scripta elegans) after exposure to UV radiation. ANIMALS: 12 yearling turtles recently removed from aestivation. PROCEDURES: Turtles were randomly allocated to 2 groups (6 turtles/group). An initial blood sample was collected from all turtles for measurement of 25-hydroxyvitamin D(3) concentrations. Turtles of 1 group were then provided no supplemental lighting, whereas turtles of the other group were exposed to full-spectrum coil bulbs at a distance of 22.86 cm. The UV-A and UV-B radiation generated by the supplemental lighting was measured by use of a radiometer-photometer at weekly intervals. Measurements were collected 2.54 and 22.86 cm from the bulb surface. The study was continued for a 4-week period. At the end of the study, a second blood sample was collected from all turtles for measurement of 25-hydroxyvitamin D(3). RESULTS: Mean +/- SD 25-hydroxyvitamin D(3) concentrations differed significantly between turtles provided supplemental UV radiation (71.7 +/- 46.9 nmol/L) and those not provided UV radiation (31.4 +/- 13.2 nmol/L). CONCLUSIONS AND CLINICAL RELEVANCE: Appropriate husbandry recommendations for raising and maintaining red-eared slider turtles should include use of sunlight that is unobstructed by UV-B filtering material or provision of an artificial source of UV-B radiation

Effects of ultraviolet radiation on plasma 25-hydroxyvitamin D3 concentrations in corn snakes (Elaphe guttata)

OBJECTIVE: To determine whether corn snakes exposed to UVB radiation have increased plasma 25-hydroxyvitamin D3 concentrations, compared with control snakes. ANIMALS: 12 corn snakes (Elaphe guttata). PROCEDURES: After an acclimation period in individual enclosures, a blood sample was collected from each snake for assessment of plasma 25-hydroxyvitamin D3 concentration. Six snakes were provided with no supplemental lighting, and 6 snakes were exposed to light from 2 full-spectrum coil bulbs. By use of a radiometer-photometer, the UVA and UVB radiation generated by the bulbs were measured in each light-treated enclosure at 3 positions at the basking surface and at 2.54 cm (1 inch) below each bulb surface; the arithmetic mean values for the 3 positions at the basking surface and each individual bulb surface were calculated immediately after the start of the study and at weekly intervals thereafter. At the end of the study (day 28), another blood sample was collected from each snake to determine plasma 25-hydroxyvitamin D3 concentration. RESULTS: Mean +/- SD plasma concentration of 25-hydroxyvitamin D3 in snakes that were provided with supplemental lighting (196 +/- 16.73 nmol/L) differed significantly from the value in control snakes (57.17 +/- 15.28 nmol/L). Mean exposure to UVA or UVB did not alter during the 4-week study period, although the amount of UVA recorded near the bulb surfaces did change significantly. CLINICAL RELEVANCE: These findings have provided important insight into the appropriate UV radiation requirements for corn snakes. Further investigation will be needed before exact husbandry requirements can be determined