Percolation and epidemics in a two-dimensional small world

Percolation on two-dimensional small-world networks has been proposed as a model for the spread of plant diseases. In this paper we give an analytic solution of this model using a combination of generating function methods and high-order series expansion. Our solution gives accurate predictions for quantities such as the position of the percolation threshold and the typical size of disease outbreaks as a function of the density of "shortcuts" in the small-world network. Our results agree with scaling hypotheses and numerical simulations for the same model.Comment: 7 pages, 3 figures, 2 table

Time-distance analysis of the emerging active region NOAA 10790

We investigate the emergence of Active Region NOAA 10790 by means of time – distance helioseismology. Shallow regions of increased sound speed at the location of increased magnetic activity are observed, with regions becoming deeper at the locations of sunspot pores. We also see a long-lasting region of decreased sound speed located underneath the region of the flux emergence, possibly relating to a temperature perturbation due to magnetic quenching of eddy diffusivity, or to a dense flux tube. We detect and track an object in the subsurface layers of the Sun characterised by increased sound speed which could be related to emerging magnetic-flux and thus obtain a provisional estimate of the speed of emergence of around 1 km s−1

Subsurface nitrate reduction under wetlands takes place in narrow superficial zones

This study aims to investigate the depth distribution of the Nitrate Reduction Potential (NRP) on a natural and a re-established wetland. The obtained NRP provides a valuable data of the driving factors affecting denitrification, the Dissimilatory Nitrate Reduction to Ammonium (DNRA) process and the performance of a re-established wetland. Intact soil cores were collected and divided in slices for the determination of Organic Matter (OM) through Loss of Ignition (LOI) as well as Dissolved Organic Carbon (DOC) and NRP spiking nitrate in batch tests. The Nitrate Reduction (NR) was fitted as a pseudo-first order rate constant (k) from where NRPs were obtained. NR took place in a narrow superficial zone showing a dropping natural logarithmic trend along depth. The main driving factor of denitrification, besides depth, was OM. Although, DOC and LOI could not express by themselves and absolute correlation with NRP, high amounts of DOC ensured enough quantity and quality of labile OM for NR. Besides, high concentration of LOI but a scarce abundance of DOC failed to drive NR. DNRA was only important in superficial samples with high contents of OM. Lastly, the high NRP of the re-established wetland confirms that wetlands can be restored satisfactorily.Preprin

The potential of pirtobrutinib in multiple B-cell malignancies

Bruton’s tyrosine kinase (BTK) is a critical downstream signaling element from the B-cell receptor (BCR) that has been effectively inhibited in B-cell cancers by irreversible, covalent inhibitors including ibrutinib and acalabrutinib. All FDA-approved covalent BTK inhibitors rely on binding to the cysteine 481 (C481) amino acid within the active site of BTK, thus rendering it inert. While covalent BTK inhibitors have been very successful in multiple B-cell malignancies, improving both overall survival and progression-free survival relative to chemoimmunotherapy in phase 3 trials, they can be limited by intolerance and disease progression. Pirtobrutinib is a novel, highly selective, and non-covalent BTK inhibitor that binds independently of C481, and in a recent, first-in-human phase 1/2 clinical trial was shown to be extremely well tolerated and lead to remissions in relapsed/refractory patients with multiple B-cell malignancies. Here, we review the pharmacologic rationale for pursuing non-covalent BTK inhibitors, the clinical need for such inhibitors, existing safety, and resistance mechanism data for pirtobrutinib, and the forthcoming clinical trials that seek to define the clinical utility of pirtobrutinib, which has the potential to fulfill multiple areas of unmet clinical need for patients with B-cell malignancies

Changes in global blocking character in recent decades

A global blocking climatology published by this group for events that occurred during the late 20th century examined a comprehensive list of characteristics that included block intensity (BI). In addition to confirming the results of other published climatologies, they found that Northern Hemisphere (NH) blocking events (1968-1998) were stronger than Southern Hemisphere (SH) blocks and winter events are stronger than summer events in both hemispheres. This work also examined the interannual variability of blocking as related to El Niño and Southern Oscillation (ENSO). Since the late 20th century, there is evidence that the occurrence of blocking has increased globally. A comparison of blocking characteristics since 1998 (1998-2018 NH; 2000-2018 SH) shows that the number of blocking events and their duration have increased significantly in both hemispheres. The blocking BI has decreased by about six percent in the NH, but there was little change in the BI for the SH events. Additionally, there is little or no change in the primary genesis regions of blocking. An examination of variability related to ENSO reveals that the NH interannual-scale variations found in the earlier work has reversed in the early 21st century. This could either be the result of interdecadal variability or a change in the climate. Interdecadal variations are examined as well

The ClpX chaperone controls autolytic splitting of Staphylococcus aureus daughter cells, but is bypassed by β-lactam antibiotics or inhibitors of WTA biosynthesis.

β-lactam antibiotics interfere with cross-linking of the bacterial cell wall, but the killing mechanism of this important class of antibiotics is not fully understood. Serendipitously we found that sub-lethal doses of β-lactams rescue growth and prevent spontaneous lysis of Staphylococcus aureus mutants lacking the widely conserved chaperone ClpX, and we reasoned that a better understanding of the clpX phenotypes could provide novel insights into the downstream effects of β-lactam binding to the PBP targets. Super-resolution imaging revealed that clpX cells display aberrant septum synthesis, and initiate daughter cell separation prior to septum completion at 30°C, but not at 37°C, demonstrating that ClpX becomes critical for coordinating the S. aureus cell cycle as the temperature decreases. FtsZ localization and dynamics were not affected in the absence of ClpX, suggesting that ClpX affects septum formation and autolytic activation downstream of Z-ring formation. Interestingly, oxacillin antagonized the septum progression defects of clpX cells and prevented lysis of prematurely splitting clpX cells. Strikingly, inhibitors of wall teichoic acid (WTA) biosynthesis that work synergistically with β-lactams to kill MRSA synthesis also rescued growth of the clpX mutant, as did genetic inactivation of the gene encoding the septal autolysin, Sle1. Taken together, our data support a model in which Sle1 causes premature splitting and lysis of clpX daughter cells unless Sle1-dependent lysis is antagonized by β-lactams or by inhibiting an early step in WTA biosynthesis. The finding that β-lactams and inhibitors of WTA biosynthesis specifically prevent lysis of a mutant with dysregulated autolytic activity lends support to the idea that PBPs and WTA biosynthesis play an important role in coordinating cell division with autolytic splitting of daughter cells, and that β-lactams do not kill S. aureus simply by weakening the cell wall