Genetic counseling workforce diversity, inclusion, and capacity in Australia and New Zealand.

Purpose: To understand diversity, inclusion, and capacity of genetic counselors (GCs) in Australasia (Australia and New Zealand).

Methods: Individuals with or working toward a GC qualification in Australasia were invited to complete an online survey, between November 2022 and March 2023. Quantitative data were analyzed using descriptive statistics, 1-sample proportion -tests, 2-sample -tests, and χ tests.

Structure of the microtubule anchoring factor NEDD1 bound to the γ-tubulin ring complex.

The γ-tubulin ring complex (γ-TuRC) is an essential multiprotein assembly, in which γ-tubulin, GCP2-6, actin, MZT1 and MZT2 form an asymmetric cone-shaped structure that provides a template for microtubule nucleation. The γ-TuRC is recruited to microtubule organizing centers (MTOCs), such as centrosomes and pre-existing mitotic spindle microtubules, via the evolutionarily-conserved attachment factor NEDD1. NEDD1 contains an N-terminal WD40 domain that binds to microtubules, and a C-terminal domain that associates with the γ-TuRC.

Dark brown carbon from wildfires: a potent snow radiative forcing agent?

Deposition of wildfire smoke on snow contributes to its darkening and accelerated snowmelt. Recent field studies have identified dark brown carbon (d-BrC) to contribute 50-75% of shortwave absorption in wildfire smoke. d-BrC is a distinct class of water-insoluble, light-absorbing organic carbon that co-exists in abundance with black carbon (BC) in snow across the world.

Allosteric activation of VCP, an AAA unfoldase, by small molecule mimicry.

The loss of function of AAA (ATPases associated with diverse cellular activities) mechanoenzymes has been linked to diseases, and small molecules that activate these proteins can be powerful tools to probe mechanisms and test therapeutic hypotheses. Unlike chemical inhibitors that can bind a single conformational state to block enzyme function, activator binding must be permissive to different conformational states needed for mechanochemistry. However, we do not know how AAA proteins can be activated by small molecules.

Structure of the γ-tubulin ring complex-capped microtubule.

Microtubules are composed of α-tubulin and β-tubulin dimers positioned head-to-tail to form protofilaments that associate laterally in varying numbers. It is not known how cellular microtubules assemble with the canonical 13-protofilament architecture, resulting in micrometer-scale α/β-tubulin tracks for intracellular transport that align with, rather than spiral along, the long axis of the filament. We report that the human ~2.

Spastin regulates anaphase chromosome separation distance and microtubule-containing nuclear tunnels.

Nuclear envelope reassembly during the final stages of each mitosis depends on disassembling spindle microtubules without disrupting chromosome separation. This process involves the transient recruitment of the ESCRT-III complex and spastin, a microtubule-severing AAA (ATPases associated with diverse cellular activities) mechanoenzyme, to late-anaphase chromosomes. However, dissecting mechanisms underlying these rapid processes, which can be completed within minutes, has been difficult.

Using a Function-First "Scout Fragment"-Based Approach to Develop Allosteric Covalent Inhibitors of Conformationally Dynamic Helicase Mechanoenzymes.

Helicases, classified into six superfamilies, are mechanoenzymes that utilize energy derived from ATP hydrolysis to remodel DNA and RNA substrates. These enzymes have key roles in diverse cellular processes, such as translation, ribosome assembly, and genome maintenance. Helicases with essential functions in certain cancer cells have been identified, and helicases expressed by many viruses are required for their pathogenicity.

Structure of the γ-tubulin ring complex-capped microtubule.

Unlabelled: Microtubules are composed of α/β-tubulin dimers positioned head-to-tail to form protofilaments that associate laterally in varying numbers. It is not known how cellular microtubules assemble with the canonical 13-protofilament architecture, resulting in micrometer-scale α/β-tubulin tracks for intracellular transport that align with, rather than spiral along, the filament's long-axis. We report that the human ∼2.

Fine-tuning chemical genetics to identify physiologic drug targets.

Genetics-based approaches can enable drug target identification in human cells. In this issue of Cell Chemical Biology, Nguyen et al. use inducible degradation of a mismatch repair protein to tune the mutation rate in HCT116 cells, thereby increasing sensitivity and selectivity in identifying resistance-conferring mutations for several cytotoxic small molecules.

Allosteric activation of VCP, a AAA unfoldase, by small molecule mimicry.

Unlabelled: The loss of function of AAA (ATPases associated with diverse cellular activities) mechanoenzymes has been linked to diseases, and small molecules that activate these proteins can be powerful tools to probe mechanisms and test therapeutic hypotheses. Unlike chemical inhibitors that can bind a single conformational state to block enzyme activity, activator binding must be permissive to different conformational states needed for enzyme function. However, we do not know how AAA proteins can be activated by small molecules.

Using a function-first 'scout fragment'-based approach to develop allosteric covalent inhibitors of conformationally dynamic helicase mechanoenzymes.

Helicases, classified into six superfamilies, are mechanoenzymes that utilize energy derived from ATP hydrolysis to remodel DNA and RNA substrates. These enzymes have key roles in diverse cellular processes, such as genome replication and maintenance, ribosome assembly and translation. Helicases with essential functions only in certain cancer cells have been identified and helicases expressed by certain viruses are required for their pathogenicity.

High-content microscopy reveals a morphological signature of bortezomib resistance.

Drug resistance is a challenge in anticancer therapy. In many cases, cancers can be resistant to the drug prior to exposure, that is, possess intrinsic drug resistance. However, we lack target-independent methods to anticipate resistance in cancer cell lines or characterize intrinsic drug resistance without a priori knowledge of its cause.

Physics-Informed Neural Networks for Solving Forward and Inverse Problems in Complex Beam Systems.

This article proposes a new framework using physics-informed neural networks (PINNs) to simulate complex structural systems that consist of single and double beams based on Euler-Bernoulli and Timoshenko theories, where the double beams are connected with a Winkler foundation. In particular, forward and inverse problems for the Euler-Bernoulli and Timoshenko partial differential equations (PDEs) are solved using nondimensional equations with the physics-informed loss function. Higher order complex beam PDEs are efficiently solved for forward problems to compute the transverse displacements and cross-sectional rotations with less than 1e-3 % error.

Observing inhibition of the SARS-CoV-2 helicase at single-nucleotide resolution.

The genome of SARS-CoV-2 encodes for a helicase (nsp13) that is essential for viral replication and highly conserved across related viruses, making it an attractive antiviral target. Here we use nanopore tweezers, a high-resolution single-molecule technique, to gain detailed insight into how nsp13 turns ATP-hydrolysis into directed motion along nucleic acid strands. We measured nsp13 both as it translocates along single-stranded DNA or unwinds double-stranded DNA.

Achieving the promise and avoiding the peril of chemical probes using genetics.

Chemical probes can be valuable tools for studying protein targets, but addressing concerns about a probe's cellular target or its specificity can be challenging. A reliable strategy is to use a mutation that does not alter a target's function but confers resistance (or sensitizes) to the inhibitor in both cellular and biochemical assays. However, challenges remain in finding such mutations.

Survey of Peritoneal Dialysis Patients' Challenges and Experiences during the COVID-19 Pandemic: A Multicenter Study in the United States.

Key Points: The adjustments made by the dialysis units during the peak of the pandemic were effective in maneuvering the challenges faced by our patients during the COVID-19 pandemic. Patients who remained on PD were satisfied with the quality of care, felt supported by the unit staff, and did not report feeling anxious or depressed.

Background: During the coronavirus disease 2019 (COVID-19) pandemic, adjustments were made to peritoneal dialysis (PD) practices in the outpatient units.

Vanishing Bile Duct Syndrome in a Patient With Recurrent Hodgkin Lymphoma.

Vanishing bile duct syndrome (VBDS) is an acquired syndrome characterized by clinical and laboratory signs of cholestasis with pathologic findings of interlobular bile duct paucity in liver biopsy specimens. VBDS can result from a variety of conditions including infections, autoimmune diseases, adverse drug reactions, and neoplastic processes. Hodgkin lymphoma (HL) is a rare cause of VBDS.

High-content microscopy reveals a morphological signature of bortezomib resistance.

Drug resistance is a challenge in anticancer therapy, particularly with targeted therapeutics and cytotoxic compounds. In many cases, cancers can be resistant to the drug prior to exposure, i.e.

Reassessing the availability of crop residue as a bioenergy resource in India: A field-survey based study.

Second-generation bioenergy, a carbon neutral or negative renewable resource, is crucial to achieving India's net-zero emission targets. Crop residues are being targeted as a bioenergy resource as they are otherwise burned on-field, leading to significant pollutant emissions. But estimating their bioenergy potential is problematic because of broad assumptions about their surplus fractions.

A nucleotide binding-independent role for γ-tubulin in microtubule capping and cell division.

The γ-tubulin ring complex (γ-TuRC) has essential roles in centrosomal and non-centrosomal microtubule organization during vertebrate mitosis. While there have been important advances in understanding γ-TuRC-dependent microtubule nucleation, γ-TuRC capping of microtubule minus-ends remains poorly characterized. Here, we utilized biochemical reconstitutions and cellular assays to characterize the human γ-TuRC's capping activity.

Primary Osseous Low-grade Myxofibrosarcoma of Metatarsal Masquerading as Enchondroma: A Case Report.

Introduction: Low-grade myxofibrosarcoma (LGMFS) is a neoplasm of soft tissues. According to the World Health Organization, LGMFS is a malignant myofibroblastic tumor arising from deep soft tissues with potential for recurrence and late metastatic spread. The incidence estimates are 0.