Isolation of a Dissimilatory Iodate-Reducing Aromatoleum sp. From a Freshwater Creek in the San Francisco Bay Area

Recent reports of dissimilatory iodate-reducing microorganisms (DIRM) have arisen from studies of bacteria in marine environments. These studies described the physiology and distribution of DIRM while also demonstrating their presence in iodine-rich marine environments. We posited that despite lower iodine concentrations, terrestrial and freshwater ecosystems should also harbor DIRM. We established numerous enrichments from coastal and freshwater environments that actively remove amended iodate. We describe the physiology and genome of a new DIRM isolate, Aromatoleum toluclasticum sp. TC-10, emerging from a freshwater creek microcosm. Like other DIRM, A. toluclasticum sp. TC-10 couples acetate oxidation to iodate reduction with a concomitant increase in the OD600. Our results indicate that A. toluclasticum sp. TC-10 performs dissimilatory iodate reduction (DIR) using the recently described iodate reductase (Idr). We provide further evidence of horizontal gene transfer of the idr genes by demonstrating the lack of Idr in the closely related (99.93% 16S rDNA sequence identity) A. toluclasticum sp. MF63 and describe the heterogeneity of the accessory proteins associated with the iodate reduction island (IRI). These observations provide additional evidence that DIR is a horizontally acquired metabolism with broad environmental distribution beyond exclusively marine environments.

Squeeze the beat: Enhancing cardiac vagal activation during resonance breathing via coherent pelvic floor recruitment. A Pilot Study.

Resonance breathing (RB) has been shown to improve psychophysiological health and performance within clinical and non-clinical populations. This is attributed to its baroreflex stimulating effects and the concomitant increase in cardiac vagal activation (CVA). Hence, developing methods that strengthen the CVA boosting effect of RB could improve its clinical effectiveness. Therefore, we assessed whether supplementing RB with coherent pelvic floor activation (PRB), which has been shown to entrain the baroreflex, yields stronger CVA than standard RB. N = 32 participants performed 5-minutes of RB and PRB, which requires to recruit the pelvic floor during inhalation and release it at the initiation of the expiration. CVA was indexed via heart rate variability using RMSSD and LF-HRV. PRB induced significantly larger RMSSD (d = 1.04) and LF-HRV (d = 0.75, ps < .001) compared to RB. Our results indicate that coherent pelvic floor recruitment during RB enhances its CVA boosting effects in healthy individuals. However, subsequent studies are warranted to evaluate whether these first findings can be replicated in individuals with compromised health, including a more comprehensive psychophysiological assessment to potentially elucidate the origin of the promising effects. Importantly, longitudinal studies need to address whether the additional CVA during PRB translates to better treatment outcomes.

Scaling of cellular proteome with ploidy

Ploidy changes are frequent in nature and contribute to evolution, functional specialization and tumorigenesis. Analysis of model organisms of different ploidies revealed that increased ploidy leads to an increase in cell and nuclear volume, reduced proliferation, metabolic changes, lower fitness, and increased genomic instability, but the underlying mechanisms remain poorly understood. To investigate how the gene expression changes with cellular ploidy, we analyzed isogenic series of budding yeasts from 1N to 4N. We show that mRNA and protein abundance scales allometrically with ploidy, with tetraploid cells showing only threefold increase in proteins compared to haploids. This ploidy-specific scaling occurs via decreased rRNA and ribosomal protein abundance and reduced translation. We demonstrate that the Tor1 activity is reduced with increasing ploidy, which leads to rRNA gene repression via a novel Tor1-Sch9-Tup1 signaling pathway. mTORC1 and S6K activity are also reduced in human tetraploid cells and the concomitant increase of the Tup1 homolog Tle1 downregulates the rDNA transcription. Our results revealed a novel conserved mTORC1-S6K-Tup1/Tle1 pathway that ensures proteome remodeling in response to increased ploidy.

Ellagic Acid Prevents α-Synuclein Aggregation and Protects SH-SY5Y Cells from Aggregated α-Synuclein-Induced Toxicity via Suppression of Apoptosis and Activation of Autophagy

Parkinson’s disease (PD) is a neurodegenerative disease characterized by the loss of dopamine neurons and the deposition of misfolded proteins known as Lewy bodies (LBs), which contain α-synuclein (α-syn). The causes and molecular mechanisms of PD are not clearly understood to date. However, misfolded proteins, oxidative stress, and impaired autophagy are believed to play important roles in the pathogenesis of PD. Importantly, α-syn is considered a key player in the development of PD. The present study aimed to assess the role of Ellagic acid (EA), a polyphenol found in many fruits, on α-syn aggregation and toxicity. Using thioflavin and seeding polymerization assays, in addition to electron microscopy, we found that EA could dramatically reduce α-syn aggregation. Moreover, EA significantly mitigated the aggregated α-syn-induced toxicity in SH-SY5Y cells and thus enhanced their viability. Mechanistically, these cytoprotective effects of EA are mediated by the suppression of apoptotic proteins BAX and p53 and a concomitant increase in the anti-apoptotic protein, BCL-2. Interestingly, EA was able to activate autophagy in SH-SY5Y cells, as evidenced by normalized/enhanced expression of LC3-II, p62, and pAKT. Together, our findings suggest that EA may attenuate α-syn toxicity by preventing aggregation and improving viability by restoring autophagy and suppressing apoptosis.

Clinically significant prostate cancer (csPCa) detection with various prostate sampling schemes based on different csPCa definitions

Background Combining targeted biopsy (TB) with systematic biopsy (SB) is currently recommended as the first-line biopsy method by the European Association of Urology (EAU) guidelines in patients diagnosed with prostate cancer (PCa) with an abnormal magnetic resonance imaging (MRI). The combined SB and TB indeed detected an additional number of patients with clinically significant prostate cancer (csPCa); however, it did so at the expense of a concomitant increase in biopsy cores. Our study aimed to evaluate if ipsilateral SB (ipsi-SB) + TB or contralateral SB (contra-SB) + TB could achieve almost equal csPCa detection rates as SB + TB using fewer cores based on a different csPCa definition. Methods Patients with at least one positive prostate lesion were prospectively diagnosed by MRI. The combination of TB and SB was conducted in all patients. We compared the csPCa detection rates of the following four hypothetical biopsy sampling schemes with those of SB + TB: SB, TB, ipsi-SB + TB, and contra-SB + TB. Results The study enrolled 279 men. The median core of SB, TB, ipsi-SB + TB, and contra-SB + TB was 10, 2, 7 and 7, respectively (P < 0.001). ipsi-SB + TB detected significantly more patients with csPCa than contra-SB + TB based on the EAU guidelines (P = 0.042). They were almost equal on the basis of the Epstein criteria (P = 1.000). Compared with SB + TB, each remaining method detected significantly fewer patients with csPCa regardless of the definition (P < 0.001) except ipsi-SB + TB on the grounds of D1 (P = 0.066). Ten additional subjects were identified with a higher Gleason score (GS) on contra-SB + TB, and only one was considered as significantly upgraded (GS = 6 on ipsi-SB + TB to a GS of 8 on contra-SB + TB). Conclusions Ipsi-SB + TB could acquire an almost equivalent csPCa detection value to SB + TB using significantly fewer cores when csPCa was defined according to the EAU guidelines. Given that there was only one significantly upgrading patient on contra-SB, our results suggested that contra-SB could be avoided.

Hormonal Characteristics of Women Receiving Ovarian Tissue Transplantation with or without Endogenous Ovarian Activity

Ovarian tissue cryopreservation (OTC) and transplantation of frozen/thawed ovarian tissue (OTT) are used for fertility preservation in girls and women. Here, we evaluated the hormonal characteristics of women with or without postmenopausal levels of FSH at the time of OTT to study differences and conditions that best support the initiation of ovarian function. A total of 74 women undergoing OTT (n = 51 with menopausal levels of FSH; n = 23 with premenopausal levels) were followed by measurements of FSH, LH, AMH, and oestradiol. Concentrations of FSH and LH returned to premenopausal levels after 20 weeks on average, with a concomitant increase in oestradiol. Despite resumption of ovarian activity, AMH concentrations were in most instances below the detection limit in the menopausal group, suggesting a low ovarian reserve. Despite a higher age in the premenopausal group, they more often experienced an AMH increase than the menopausal group, suggesting that conditions in the premenopausal ovary better sustain follicle survival, perhaps due to the higher concentrations of oestradiol. Collectively, this study highlights the need for improving follicle survival after OTT. Age and the amount of tissue transplanted are important factors that influence the ability to regain ovarian activity and levels of FSH may need to be downregulated and oestradiol increased prior to OTT.

High-Pressure Processing on Whole and Peeled Potatoes: Influence on Polyphenol Oxidase, Antioxidants, and Glycaemic Indices

Polyphenol oxidase (PPO) inactivation in five whole and peeled Irish potato cultivars was investigated using high-pressure processing (HPP) at 400 MPa and 600 MPa for 3 min. PPO activity was significantly lower in most of the HPP-treated samples, while the highest PPO inactivation was observed after HPP at 600 MPa. No significant (p > 0.05) changes were observed on the total phenolic content and antioxidant activity of all the HPP-treated potatoes. Regarding individual phenolic acids, chlorogenic acid was decreased significantly (p < 0.05) in all studied varieties with a concomitant increase (p < 0.05) in caffeic and quinic acid. Similarly, ferulic acid was also increased (p < 0.05) in all studied varieties after the HPP treatment, while there was a variation in rutin and 4-coumaric acid levels depending on the cultivar and the sample type. Anthocyanins in the coloured whole potato varieties (i.e., Kerr’s Pink and Rooster), tentatively identified as pelargonidin-O-ferulorylrutinoside-O-hexoside and pelargonidin-O-rutinoside-O-hexoside, also exhibited significantly (p < 0.05) higher levels in the HPP-treated samples as opposed to those untreated. Glycaemic indices of the potatoes treated with HPP did not differ with the corresponding untreated cultivars.

Comparative sphingolipidomic analysis reveals significant differences between doxorubicin-sensitive and -resistance MCF-7 cells

Drug resistance is responsible for the failure of many available anticancer drugs. Several studies have demonstrated the association between the alteration in sphingolipids (SPLs) and the development of drug resistance. To investigate the association between SPLs metabolism and doxorubicin (dox)-resistance in MCF-7 cells, a comparative sphingolipidomics analysis between dox-sensitive (parental) and -resistant MCF-7 cell lines along with validation by gene expression analysis were conducted. A total of 31 SPLs representing 5 subcategories were identified. The data obtained revealed that SPLs were clustered into two groups differentiating parental from dox-resistant cells. Eight SPLs were significantly altered in response to dox-resistance including SM (d18:1/16), SM (d18:1/24:2), SM (d18:1/24:0), SM (d18:1/20:0), SM (d18:1/23:1), HexCer (d18:1/24:0), SM (d18:1/15:0), DHSM (d18:0/20:0). The current study is the first to conclusively ascertain the potential involvement of dysregulated SPLs in dox-resistance in MCF-7 cells. SPLs metabolism in dox-resistant MCF-7 cells is oriented toward the downregulation of ceramides (Cer) and the concomitant increase in sphingomyelin (SM). Gene expression analysis has revealed that dox-resistant cells tend to escape from the Cer-related apoptosis by the activation of SM-Cer and GluCer-LacCer-ganglioside pathways. The enzymes that were correlated to the alteration in SPLs metabolism of dox-resistant MCF-7 cells and significantly altered in gene expression can represent potential targets that can represent a winning strategy for the future development of promising anticancer drugs.

Impact of the COVID-19 pandemic on tuberculosis national reference laboratory services in the WHO European Region, March to November 2020

We assessed the impact of COVID-19 on diagnostic services for tuberculosis (TB) by national reference laboratories in the WHO European Region. Of 35 laboratories, 30 reported declines in TB sample numbers, amounting up to > 50% of the pre-COVID-19 volumes. Sixteen reported reagent or consumable shortages. Nineteen reallocated ressources to SARS-CoV-2 testing, resulting in an overall increase in workload, largely without a concomitant increase in personnel (n = 14). This poses a risk to meeting the 2025 milestones of the End TB Strategy.