SOME HEAT EXPERIMENTS IMPLICATING THE EXISTENCE OF A SUBTLE ENERGY

Wilhelm Reich claimed that there existed a cosmic energy, orgone which could be accumulated in a wooden cabinet lined with sheet metal. The experiments in this paper utilized an orgone accumulator (Orac) made from a sheet metal funnel surrounded by sawdust in a cardboard box. The non-Orac control was a similar-sized plastic funnel also surrounded by sawdust and sitting next to the Orac in the same box. The relative responsiveness of the Orac and non-Orac to the heat of a warming plate was investigated in 4 experiments. On initial exposure to the heat from the warming plate in Experiment 1, the temperature of the Orac (Tl) rose more quickly than that of the non-Orac (T2). This was because the metallic funnel was more reactive to heat than the plastic one. Tl also cooled down faster than T2 when the heat was shut off because the metallic funnel was more reactive to heat loss. In this experiment, Tl, T2 and TI-T2 (Td) correlated significantly positvely with each other. In contrast to Experiment 1, where the heat was switched off when Tl and T2 reached a maximum, the warming place in Experiments 2, 3 and 4 was left on for 39 days, 36 days, and 22 months respectively. In these 3 experiments, Tl and T2 correlated significantly positvely with each other as in Experiment 1. However, in contrast to Experiment 1, Td correlated significantly negatively with Tl and T2 in Experiments 2, 3 and 4, indicating that Tl was less reactive than T2, an anomalous finding explained by implicating the cosmic orgone energy. Experiments were also conducted in which T d was used to measure local variations in the cosmic orgone as well as more distant ones, for example, those possibly related to distance from the sun

The Molecular Chaperone Hsp90α Is Required for Meiotic Progression of Spermatocytes beyond Pachytene in the Mouse

The molecular chaperone Hsp90 has been found to be essential for viability in all tested eukaryotes, from the budding yeast to Drosophila. In mammals, two genes encode the two highly similar and functionally largely redundant isoforms Hsp90α and Hsp90β. Although they are co-expressed in most if not all cells, their relative levels vary between tissues and during development. Since mouse embryos lacking Hsp90β die at implantation, and despite the fact that Hsp90 inhibitors being tested as anti-cancer agents are relatively well tolerated, the organismic functions of Hsp90 in mammals remain largely unknown. We have generated mouse lines carrying gene trap insertions in the Hsp90α gene to investigate the global functions of this isoform. Surprisingly, mice without Hsp90α are apparently normal, with one major exception. Mutant male mice, whose Hsp90β levels are unchanged, are sterile because of a complete failure to produce sperm. While the development of the male reproductive system appears to be normal, spermatogenesis arrests specifically at the pachytene stage of meiosis I. Over time, the number of spermatocytes and the levels of the meiotic regulators and Hsp90 interactors Hsp70-2, NASP and Cdc2 are reduced. We speculate that Hsp90α may be required to maintain and to activate these regulators and/or to disassemble the synaptonemal complex that holds homologous chromosomes together. The link between fertility and Hsp90 is further supported by our finding that an Hsp90 inhibitor that can cross the blood-testis barrier can partially phenocopy the genetic defects

Dicer1 Depletion in Male Germ Cells Leads to Infertility Due to Cumulative Meiotic and Spermiogenic Defects

Background: Spermatogenesis is a complex biological process that requires a highly specialized control of gene expression. In the past decade, small non-coding RNAs have emerged as critical regulators of gene expression both at the transcriptional and post-transcriptional level. DICER1, an RNAse III endonuclease, is essential for the biogenesis of several classes of small RNAs, including microRNAs (miRNAs) and endogenous small interfering RNAs (endo-siRNAs), but is also critical for the degradation of toxic transposable elements. In this study, we investigated to which extent DICER1 is required for germ cell development and the progress of spermatogenesis in mice.Principal Findings: We show that the selective ablation of Dicer1 at the early onset of male germ cell development leads to infertility, due to multiple cumulative defects at the meiotic and post-meiotic stages culminating with the absence of functional spermatozoa. Alterations were observed in the first spermatogenic wave and include delayed progression of spermatocytes to prophase I and increased apoptosis, resulting in a reduced number of round spermatids. The transition from round to mature spermatozoa was also severely affected, since the few spermatozoa formed in mutant animals were immobile and misshapen, exhibiting morphological defects of the head and flagellum. We also found evidence that the expression of transposable elements of the SINE family is up-regulated in Dicer1-depleted spermatocytes.Conclusions/Significance: Our findings indicate that DICER1 is dispensable for spermatogonial stem cell renewal and mitotic proliferation, but is required for germ cell differentiation through the meiotic and haploid phases of spermatogenesis

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

How well do covariates perform when adjusting for sampling bias in online COVID-19 research? Insights from multiverse analyses

: COVID-19 research has relied heavily on convenience-based samples, which-though often necessary-are susceptible to important sampling biases. We begin with a theoretical overview and introduction to the dynamics that underlie sampling bias. We then empirically examine sampling bias in online COVID-19 surveys and evaluate the degree to which common statistical adjustments for demographic covariates successfully attenuate such bias. This registered study analysed responses to identical questions from three convenience and three largely representative samples (total N = 13,731) collected online in Canada within the International COVID-19 Awareness and Responses Evaluation Study ( www.icarestudy.com ). We compared samples on 11 behavioural and psychological outcomes (e.g., adherence to COVID-19 prevention measures, vaccine intentions) across three time points and employed multiverse-style analyses to examine how 512 combinations of demographic covariates (e.g., sex, age, education, income, ethnicity) impacted sampling discrepancies on these outcomes. Significant discrepancies emerged between samples on 73% of outcomes. Participants in the convenience samples held more positive thoughts towards and engaged in more COVID-19 prevention behaviours. Covariates attenuated sampling differences in only 55% of cases and increased differences in 45%. No covariate performed reliably well. Our results suggest that online convenience samples may display more positive dispositions towards COVID-19 prevention behaviours being studied than would samples drawn using more representative means. Adjusting results for demographic covariates frequently increased rather than decreased bias, suggesting that researchers should be cautious when interpreting adjusted findings. Using multiverse-style analyses as extended sensitivity analyses is recommended

How well do covariates perform when adjusting for sampling bias in online COVID-19 research? Insights from multiverse analyses

COVID-19 research has relied heavily on convenience-based samples, which—though often necessary—are susceptible to important sampling biases. We begin with a theoretical overview and introduction to the dynamics that underlie sampling bias. We then empirically examine sampling bias in online COVID-19 surveys and evaluate the degree to which common statistical adjustments for demographic covariates successfully attenuate such bias. This registered study analysed responses to identical questions from three convenience and three largely representative samples (total N = 13,731) collected online in Canada within the International COVID-19 Awareness and Responses Evaluation Study (www.icarestudy.com). We compared samples on 11 behavioural and psychological outcomes (e.g., adherence to COVID-19 prevention measures, vaccine intentions) across three time points and employed multiverse-style analyses to examine how 512 combinations of demographic covariates (e.g., sex, age, education, income, ethnicity) impacted sampling discrepancies on these outcomes. Significant discrepancies emerged between samples on 73% of outcomes. Participants in the convenience samples held more positive thoughts towards and engaged in more COVID-19 prevention behaviours. Covariates attenuated sampling differences in only 55% of cases and increased differences in 45%. No covariate performed reliably well. Our results suggest that online convenience samples may display more positive dispositions towards COVID-19 prevention behaviours being studied than would samples drawn using more representative means. Adjusting results for demographic covariates frequently increased rather than decreased bias, suggesting that researchers should be cautious when interpreting adjusted findings. Using multiverse-style analyses as extended sensitivity analyses is recommended

PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling

BACKGROUND: PCA3 is a non-coding RNA (ncRNA) that is highly expressed in prostate cancer (PCa) cells, but its functional role is unknown. To investigate its putative function in PCa biology, we used gene expression knockdown by small interference RNA, and also analyzed its involvement in androgen receptor (AR) signaling. METHODS: LNCaP and PC3 cells were used as in vitro models for these functional assays, and three different siRNA sequences were specifically designed to target PCA3 exon 4. Transfected cells were analyzed by real-time qRT-PCR and cell growth, viability, and apoptosis assays. Associations between PCA3 and the androgen-receptor (AR) signaling pathway were investigated by treating LNCaP cells with 100 nM dihydrotestosterone (DHT) and with its antagonist (flutamide), and analyzing the expression of some AR-modulated genes (TMPRSS2, NDRG1, GREB1, PSA, AR, FGF8, CdK1, CdK2 and PMEPA1). PCA3 expression levels were investigated in different cell compartments by using differential centrifugation and qRT-PCR. RESULTS: LNCaP siPCA3-transfected cells significantly inhibited cell growth and viability, and increased the proportion of cells in the sub G0/G1 phase of the cell cycle and the percentage of pyknotic nuclei, compared to those transfected with scramble siRNA (siSCr)-transfected cells. DHT-treated LNCaP cells induced a significant upregulation of PCA3 expression, which was reversed by flutamide. In siPCA3/LNCaP-transfected cells, the expression of AR target genes was downregulated compared to siSCr-transfected cells. The siPCA3 transfection also counteracted DHT stimulatory effects on the AR signaling cascade, significantly downregulating expression of the AR target gene. Analysis of PCA3 expression in different cell compartments provided evidence that the main functional roles of PCA3 occur in the nuclei and microsomal cell fractions. CONCLUSIONS: Our findings suggest that the ncRNA PCA3 is involved in the control of PCa cell survival, in part through modulating AR signaling, which may raise new possibilities of using PCA3 knockdown as an additional therapeutic strategy for PCa control