Light-induced degradation of phyA is promoted by transfer of the photoreceptor into the nucleus

Higher plants possess multiple members of the phytochrome family of red, far-red light sensors to modulate plant growth and development according to competition from neighbors. The phytochrome family is composed of the light-labile phyA and several light-stable members (phyB-phyE in Arabidopsis). phyA accumulates to high levels in etiolated seedlings and is essential for young seedling establishment under a dense canopy. In photosynthetically active seedlings high levels of phyA counteract the shade avoidance response. phyA levels are maintained low in light-grown plants by a combination of light-dependent repression of PHYA transcription and light-induced proteasome-mediated degradation of the activated photoreceptor. Light-activated phyA is transported from the cytoplasm where it resides in darkness to the nucleus where it is needed for most phytochrome-induced responses. Here we show that phyA is degraded by a proteasome-dependent mechanism both in the cytoplasm and the nucleus. However, phyA degradation is significantly slower in the cytoplasm than in the nucleus. In the nucleus phyA is degraded in a proteasome-dependent mechanism even in its inactive Pr (red light absorbing) form, preventing the accumulation of high levels of nuclear phyA in darkness. Thus, light-induced degradation of phyA is in part controlled by a light-regulated import into the nucleus where the turnover is faster. Although most phyA responses require nuclear phyA it might be useful to maintain phyA in the cytoplasm in its inactive form to allow accumulation of high levels of the light sensor in etiolated seedling

A Primer on the Differential Calculus of 3D Orientations

The proper handling of 3D orientations is a central element in many optimization problems in engineering. Unfortunately many researchers and engineers struggle with the formulation of such problems and often fall back to suboptimal solutions. The existence of many different conventions further complicates this issue, especially when interfacing multiple differing implementations. This document discusses an alternative approach which makes use of a more abstract notion of 3D orientations. The relative orientation between two coordinate systems is primarily identified by the coordinate mapping it induces. This is combined with the standard exponential map in order to introduce representation-independent and minimal differentials, which are very convenient in optimization based methods

The evolutionary conserved BER1 gene is involved in microtubule stability in yeast

In yeast, microtubules are dynamic filaments necessary for spindle and nucleus positioning, as well as for proper chromosome segregation. We identify a function for the yeast gene BER1 (Benomyl REsistant 1) in microtubule stability. BER1 belongs to an evolutionary conserved gene family whose founding member Sensitivity to Red light Reduced is involved in red-light perception and circadian rhythms in Arabidopsis. Here, we present data showing that the ber1Δ mutant is affected in microtubule stability, particularly in presence of microtubule-depolymerising drugs. The pattern of synthetic lethal interactions obtained with the ber1Δ mutant suggests that Ber1 may function in N-terminal protein acetylation. Our work thus suggests that microtubule stability might be regulated through this post-translational modification on yet-to-be determined protein

Phosphorylation of phytochrome B inhibits light-induced signaling via accelerated dark reversion in Arabidopsis

The photoreceptor phytochrome B (phyB) interconverts between the biologically active Pfr (lmax = 730 nm) and inactive Pr (lmax = 660 nm) forms in a red/far-red–dependent fashion and regulates, as molecular switch, many aspects of lightdependent development in Arabidopsis thaliana. phyB signaling is launched by the biologically active Pfr conformer and mediated by specific protein–protein interactions between phyB Pfr and its downstream regulatory partners, whereas conversion of Pfr to Pr terminates signaling. Here, we provide evidence that phyB is phosphorylated in planta at Ser-86 located in the N-terminal domain of the photoreceptor. Analysis of phyB-9 transgenic plants expressing phospho-mimic and nonphosphorylatable phyB–yellow fluorescent protein (YFP) fusions demonstrated that phosphorylation of Ser-86 negatively regulates all physiological responses tested. The Ser86Asp and Ser86Ala substitutions do not affect stability, photoconversion, and spectral properties of the photoreceptor, but light-independent relaxation of the phyBSer86Asp Pfr into Pr, also termed dark reversion, is strongly enhanced both in vivo and in vitro. Faster dark reversion attenuates red light–induced nuclear import and interaction of phyBSer86Asp-YFP Pfr with the negative regulator PHYTOCHROME INTERACTING FACTOR3 compared with phyB–green fluorescent protein. These data suggest that accelerated inactivation of the photoreceptor phyB via phosphorylation of Ser-86 represents a new paradigm for modulating phytochrome-controlled signaling

The Role of Primary Retroperitoneal Lymph Node Dissection in the Treatment of Stage II Seminoma

Purpose of review Stage II seminoma is responsive to chemo- or radiotherapy with a progression-free survival of 87–95% at 5 years but at the cost of short- and long-term toxicity. After evidence about these long-term morbidities emerged, four surgical cohorts investigating the role of retroperitoneal lymph node dissection (RPLND) as a treatment option for stage II disease were initiated. Recent findings Currently, two RPLND series have been published as a complete report, while data from other series have only been published as congress abstracts. In series without adjuvant chemotherapy, recurrence rates ranged from 13% to 30% after follow-ups of 21–32 months. In those receiving RPLND and adjuvant chemotherapy, the recurrence rate was 6% after a mean follow-up of 51 months. Across all trials, recurrent disease was treated with systemic chemotherapy (22/25), surgery (2/25), and radiotherapy (1/25). The rate of pN0 disease after RPLND varied between 4% and 19%. Postoperative complications were reported in 2–12%, while antegrade ejaculation was maintained in 88–95% of patients. Median length of stay ranged from 1 to 6 days. Summary In men with clinical stage II seminoma, RPLND is a safe and promising treatment option. Further research is needed to determine the risk of relapse and to personalize treatment options based on patient-specific risk factors

Plasma membrane H⁺ -ATPase regulation is required for auxin gradient formation preceding phototropic growth.

Phototropism is a growth response allowing plants to align their photosynthetic organs toward incoming light and thereby to optimize photosynthetic activity. Formation of a lateral gradient of the phytohormone auxin is a key step to trigger asymmetric growth of the shoot leading to phototropic reorientation. To identify important regulators of auxin gradient formation, we developed an auxin flux model that enabled us to test in silico the impact of different morphological and biophysical parameters on gradient formation, including the contribution of the extracellular space (cell wall) or apoplast. Our model indicates that cell size, cell distributions, and apoplast thickness are all important factors affecting gradient formation. Among all tested variables, regulation of apoplastic pH was the most important to enable the formation of a lateral auxin gradient. To test this prediction, we interfered with the activity of plasma membrane H⁺ -ATPases that are required to control apoplastic pH. Our results show that H⁺ -ATPases are indeed important for the establishment of a lateral auxin gradient and phototropism. Moreover, we show that during phototropism, H⁺ -ATPase activity is regulated by the phototropin photoreceptors, providing a mechanism by which light influences apoplastic pH

Comparison of strategies to reduce meticillin-resistant Staphylococcus aureus rates in surgical patients: a controlled multicentre intervention trial.

Objective: To compare the effect of two strategies (enhanced hand hygiene vs meticillin-resistant Staphylococcus aureus (MRSA) screening and decolonisation) alone and in combination on MRSA rates in surgical wards. Design: Prospective, controlled, interventional cohort study, with 6-month baseline, 12-month intervention and 6-month washout phases. Setting: 33 surgical wards of 10 hospitals in nine countries in Europe and Israel. Participants: All patients admitted to the enrolled wards for more than 24 h. Interventions: The two strategies compared were (1) enhanced hand hygiene promotion and (2) universal MRSA screening with contact precautions and decolonisation (intranasal mupirocin and chlorhexidine bathing) of MRSA carriers. Four hospitals were assigned to each intervention and two hospitals combined both strategies, using targeted MRSA screening. Outcome measures: Monthly rates of MRSA clinical cultures per 100 susceptible patients (primary outcome) and MRSA infections per 100 admissions (secondary outcome). Planned subgroup analysis for clean surgery wards was performed. Results: After adjusting for clustering and potential confounders, neither strategy when used alone was associated with significant changes in MRSA rates. Combining both strategies was associated with a reduction in the rate of MRSA clinical cultures of 12% per month (adjusted incidence rate ratios (aIRR) 0.88, 95% CI 0.79 to 0.98). In clean surgery wards, strategy 2 (MRSA screening, contact precautions and decolonisation) was associated with decreasing rates of MRSA clinical cultures (15% monthly decrease, aIRR 0.85, 95% CI 0.74 to 0.97) and MRSA infections (17% monthly decrease, aIRR 0.83, 95% CI 0.69 to 0.99). Conclusions: In surgical wards with relatively low MRSA prevalence, a combination of enhanced standard and MRSA-specific infection control approaches was required to reduce MRSA rates. Implementation of single interventions was not effective, except in clean surgery wards where MRSA screening coupled with contact precautions and decolonisation was associated with significant reductions in MRSA clinical culture and infection rates. Trial registration clinicaltrials.gov identifier: NCT0068586

Patents as Early Indicators of Technology and Investment Trends: Analyzing the Microbiome Space as a Case Study

The human microbiome is the collective of microbes living in symbiosis on and within humans. Modulating its composition and function has become an attractive means for the prevention and treatment of a variety of diseases including cancer. Since the initiation of the human microbiome project in 2007, the number of academic publications and active patent families around the microbiome has grown exponentially. Screening patent databases can be useful for the early detection and the tracking of new technology trends. However, it is not sufficient to assess portfolio sizes because emerging players with small but high-quality patent portfolios will be missed within the noise of large but low-quality portfolio owners. Here we used the consolidated database and software tool PatentSight to benchmark patent portfolios, and to analyze key patent owners and innovators in the microbiome space. Our study shows how in-depth patent analyses combining qualitative and quantitative parameters can identify actionable early indicators of technology and investment trends from large patent datasets

Anterior Sphincter-sparing Suturing of the Vesicourethral Anastomosis During Robotic-assisted Laparoscopic Radical Prostatectomy

Background: Continence is an important functional outcome after robotic-assisted laparoscopic radical prostatectomy (RARP), and modifications of the surgical technique may improve outcomes. Objective: To illustrate a novel RARP technique and to describe the observed continence outcomes. Design setting and participants: A retrospective study of men treated with RARP between 2017 and 2021 was conducted. Surgical procedure: During RARP, periprostatic structures are preserved, the intraprostatic urethra is partially spared, and the anterior anastomosis stitches involve the plexus structures but not the anterior urethra. Measurements: A descriptive analysis of the pathological, functional, and short-term oncological outcomes was performed. Results and limitations: Of 640 men, 448 (70%) with at least 1 yr of follow-up and a median age of 66 yr were included. The median operative time was 270 min and the prostatic volume 52 ml. The transurethral catheter was removed after a median of 3 d, and leakage of urine in the first 24 h after catheter removal was observed in 66/448 patients (15%). Positive surgical margins were reported in 104/448 (23%). Prostate-specific antigen persistence after prostatectomy was observed in 26/448 (6%). During a median follow-up of 2 yr (interquartile range 1-3 yr), the biochemical recurrence after prostatectomy was observed in 19/448 patients (4%). One year after prostatectomy, 406/448 patients (91%) were continent and required no pad at all, while 42/448 (9%) required at least one pad per day. Conclusions: Not stitching the anterior urethra is a novel technical modification and may improve continence outcomes. Patient summary: We describe a novel way to stitch the bladder neck to the urethra after removal of the prostate using a surgical robotic system. Our technique appeared safe, with promising urinary continence results