You might expect to see wheelchairs and walking frames in the corridors of an aged care facility, but you might not expect to see a 850-kilogram horse.

An Aboriginal corporation in the Kimberley is set to become the first to commercialise the breeding of native freshwater prawns.

After 25 years as a sniper in war zones, Robert later went on to photograph road fatalities. After being plagued by anxiety, depression and flashbacks, he has finally found peace with the power of painting.

Lego is being used in both informal and clinical sessions to improve the communication and cooperation skills of children with autism.

People who experience homelessness are more likely to be exposed to trauma, but experts say creative therapies could help them heal.

A teenager from Byron Bay says regularly seeing a psychologist has helped him tackle crippling anxiety. The only problem is he can't afford to keep going.

Taking the waters of a mineral pool is a long, human tradition, and today it is often grey nomads seeking out their reputed healing and bubbling waters.

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(United States Federal Circuit) - Affirmed that a pharmaceutical company's patent claims in a multiple sclerosis drug were invalid for obviousness. Several competitors seeking to market a generic version of the same drug raised the issue of obviousness when the company sued them for infringement. In a 2-1 decision, the Federal Circuit affirmed that the patent claims in question were invalid.

(United States Federal Circuit) - Affirmed that a pharmaceutical company's patent claims in a multiple sclerosis drug were invalid for obviousness. Several competitors seeking to market a generic version of the same drug raised the issue of obviousness when the company sued them for infringement. In a 2-1 decision, the Federal Circuit affirmed that the patent claims in question were invalid.

(United States Federal Circuit) - Affirmed that a pharmaceutical company's patent claims in a multiple sclerosis drug were invalid for obviousness. Several competitors seeking to market a generic version of the same drug raised the issue of obviousness when the company sued them for infringement. In a 2-1 decision, the Federal Circuit affirmed that the patent claims in question were invalid.

(United States First Circuit) - Affirming the district court dismissal of a case in which a class of purchasers of securities issued by a drug company that the investors said recklessly misled them about their target date for submitting an application to the Food and Drug Administration for a drug approval because the court did not err in finding that they had failed to state a claim.

(United States Ninth Circuit) - Reversed in part the dismissal of a securities fraud class action alleging that a biotechnology firm misrepresented to investors the status of a clinical drug trial. An investor brought this suit contending that the company and certain top executives violated Section 10(b) of the Securities Exchange Act of 1934. On appeal, the Ninth Circuit held that the district court erred in part in dismissing the complaint for failure to state a claim. The panel also ruled that the district court abused its discretion in judicially noticing certain facts and in incorporating certain documents into the complaint.

(United States Seventh Circuit) - Held that a manufacturer breached its contractual agreement with a distributor in the medical-supply industry. Affirmed a bench trial judgment, in a case involving distribution rights to a special type of hospital bed.

Whether mutations in cancer driver genes directly affect cancer immune phenotype and T cell immunity remains a standing question. ARID1A is a core member of the polymorphic BRG/BRM-associated factor chromatin remodeling complex. ARID1A mutations occur in human cancers and drive cancer development. Here, we studied the molecular, cellular, and clinical impact of ARID1A aberrations on cancer immunity. We demonstrated that ARID1A aberrations resulted in limited chromatin accessibility to IFN-responsive genes, impaired IFN gene expression, anemic T cell tumor infiltration, poor tumor immunity, and shortened host survival in many human cancer histologies and in murine cancer models. Impaired IFN signaling was associated with poor immunotherapy response. Mechanistically, ARID1A interacted with EZH2 via its carboxyl terminal and antagonized EZH2-mediated IFN responsiveness. Thus, the interaction between ARID1A and EZH2 defines cancer IFN responsiveness and immune evasion. Our work indicates that cancer epigenetic driver mutations can shape cancer immune phenotype and immunotherapy.

An in-depth understanding of immune escape mechanisms in cancer is likely to lead to innovative advances in immunotherapeutic strategies. However, much remains unknown regarding these mechanisms and how they impact immunotherapy resistance. Using several preclinical tumor models as well as clinical specimens, we identified a mechanism whereby CD8+ T cell activation in response to programmed cell death 1 (PD-1) blockade induced a programmed death ligand 1/NOD-, LRR-, and pyrin domain–containing protein 3 (PD-L1/NLRP3) inflammasome signaling cascade that ultimately led to the recruitment of granulocytic myeloid-derived suppressor cells (PMN-MDSCs) into tumor tissues, thereby dampening the resulting antitumor immune response. The genetic and pharmacologic inhibition of NLRP3 suppressed PMN-MDSC tumor infiltration and significantly augmented the efficacy of anti–PD-1 antibody immunotherapy. This pathway therefore represents a tumor-intrinsic mechanism of adaptive resistance to anti–PD-1 checkpoint inhibitor immunotherapy and is a promising target for future translational research.

1. AOC insists opportunity knocks for Australia's 2032 Olympic bid  Sydney Morning Herald
2. Tokyo Olympics could be the greatest ever after the coronavirus pandemic, says AOC president John Coates  ABC News
3. Sport boss claims hosting the Olympics could pull Australia out of a post-coronavirus recession  Daily Mail
4. AOC CEO looking at great sporting decade  7NEWS.com.au
5. Channel 7 sweats as Olympics plans still up in the air for 2021  Herald Sun
6. View Full coverage on Google News

We rank the 20 best Australian TV characters of all time  Herald Sun

1. Readers respond to the COVIDSafe app's launch  Sydney Morning Herald
2. Australian Gov releases source code for CovidSafe app as promised  techAU
3. Government's lack of honesty on virus app is a problem  The New Daily
4. What You Should Know About COVIDSafe's Issues And Bluetooth-Related Risks  Gizmodo Australia
5. Covidsafe app: how to download Australia’s coronavirus contact tracing app, how it works, what it does and problems  The Guardian
6. View Full coverage on Google News

1. Tributes flow after death of veteran journalist Frank Crook  Sydney Morning Herald
2. Editor, broadcaster, raconteur and writer’s writer Frank Crook dies  Daily Telegraph
3. View Full coverage on Google News

1. Laid bare: How the Dean Laidley story reveals cultural change  Sydney Morning Herald
2. Dean Laidley police photo leak: Fourth officer suspended  NEWS.com.au
3. 'Gross stupidity': Fresh investigation into Dean Laidley photo leak  Yahoo Sport Australia
4. Vic watchdog to probe leaked Laidley pics  AFL
5. IBAC to investigate leaked Laidley photos  Yass Tribune
6. View Full coverage on Google News

Systematic review produced by the EPPI-Centre in 2015.This systematic review aimed to evaluate the effect of HAART and ARV monotherapy on liver disease progression and liver-related mortality in individuals co-infected with HIV and hepatitis C, including in patients with haemophilia.

This patented therapeutic compound effectively treats both male and female sexual dysfunction. Because it targets the central nervous system, it may not have the negative cardiovascular side effects of existing sexual dysfunction therapies that target the vascular system. This patented therapeutic was discovered through collaboration of a medical doctor with a research chemist, and is currently in Phase 2B clinical trials for males in order to obtain FDA approval.

Hey there. Today I’d like to talk about SHOPPING. Like a lot of folks, I’m worried about my favorite small local shops and restaurants who are having to shut down during this crisis. I’m also REALLY worried about my favorite convention, SCA, and Ren Faire vendors, who’ve basically had all their events and income streams […]

This device is FDA-cleared for US sales, US patented and patent pending in other countries, and medically certified in Europe. It treats oncologic and neuropathic pain through a biophysical rather than biochemical approach. The non-invasive device is designed to create self-like neurons by applying surface electrodes to the skin to simultaneously treat multiple pain areas.

go to the CTI web site

Applied Behavior Analysis is administered frequently to 0-3-year-olds in the state’s Early Intervention system.

How the soothing action of knitting calms my stress and fears -- one in a series of dispatches from the pandemic.

Julio Teheran parted ways with the Braves, who had helped develop him since he was 16 in Colombia. The 29-year-old starts over with the Angels this spring.

My therapist was pushing me to date more, which is hard when you're a teacher and can't go out "on a school night." But I'm getting myself out there. L.A. traffic willing.

Miles de profesionales médicos extranjeros en un limbo inmigratorio

'Bad Therapy' stars Michaela Watkins as a devious couples therapist preying on wealthy Westsiders.

With concerts cancelled and album releases amiss, musicians with mental health issues are struggling with the stress and uncertainty from the COVID-19 pandemic.

San Cha is a queer Latina musician whose new album, 'La Luz de la Esperanza,' is a musical telenovela that reimagines rancheras with a gothic edge.

Yesterday, Prime Minister Boris Johnson told an international video conference that we face a battle of "humanity against the virus". How right that is - and the battle has started. According to Professor Nicholas Hart, one of the doctors who saved Mr Johnson's life, "COVID-19 is this generation's polio."

As confetti floated through the air, a baby boy and his family celebrated his final chemotherapy treatment in time to go home before his first birthday. According to KSAZ, young Aaron has been battling a rare form of cancer called acute megakaryoblastic leukemia since he was four months old. Aaron was a patient at Duke…

The post 10-Month-Old Gets Heartwarming Celebration from Hospital Staff After Finishing Chemotherapy appeared first on The Western Journal.

Heterotrimeric G proteins are the core upstream elements that transduce and amplify the cellular signals from G protein–coupled receptors (GPCRs) to intracellular effectors. GPCRs are the largest family of membrane proteins encoded in the human genome and are the targets of about one-third of prescription medicines. However, to date, no single therapeutic agent exerts its effects via perturbing heterotrimeric G protein function, despite a plethora of evidence linking G protein malfunction to human disease. Several recent studies have brought to light that the Gq family–specific inhibitor FR900359 (FR) is unexpectedly efficacious in silencing the signaling of Gq oncoproteins, mutant Gq variants that mostly exist in the active state. These data not only raise the hope that researchers working in drug discovery may be able to potentially strike Gq oncoproteins from the list of undruggable targets, but also raise questions as to how FR achieves its therapeutic effect. Here, we place emphasis on these recent studies and explain why they expand our pharmacological armamentarium for targeting Gq protein oncogenes as well as broaden our mechanistic understanding of Gq protein oncogene function. We also highlight how this novel insight impacts the significance and utility of using G(q) proteins as targets in drug discovery efforts.

Treatment of patients with triple-negative breast cancer (TNBC) is limited by a lack of effective molecular therapies targeting this disease. Recent studies have identified metabolic alterations in cancer cells that can be targeted to improve responses to standard-of-care chemotherapy regimens. Using MDA-MB-468 and SUM-159PT TNBC cells, along with LC-MS/MS and HPLC metabolomics profiling, we found here that exposure of TNBC cells to the cytotoxic chemotherapy drugs cisplatin and doxorubicin alter arginine and polyamine metabolites. This alteration was because of a reduction in the levels and activity of a rate-limiting polyamine biosynthetic enzyme, ornithine decarboxylase (ODC). Using gene silencing and inhibitor treatments, we determined that the reduction in ODC was mediated by its negative regulator antizyme, targeting ODC to the proteasome for degradation. Treatment with the ODC inhibitor difluoromethylornithine (DFMO) sensitized TNBC cells to chemotherapy, but this was not observed in receptor-positive breast cancer cells. Moreover, TNBC cell lines had greater sensitivity to single-agent DFMO, and ODC levels were elevated in TNBC patient samples. The alterations in polyamine metabolism in response to chemotherapy, as well as DFMO-induced preferential sensitization of TNBC cells to chemotherapy, reported here suggest that ODC may be a targetable metabolic vulnerability in TNBC.

Heterotrimeric G proteins are the core upstream elements that transduce and amplify the cellular signals from G protein–coupled receptors (GPCRs) to intracellular effectors. GPCRs are the largest family of membrane proteins encoded in the human genome and are the targets of about one-third of prescription medicines. However, to date, no single therapeutic agent exerts its effects via perturbing heterotrimeric G protein function, despite a plethora of evidence linking G protein malfunction to human disease. Several recent studies have brought to light that the Gq family–specific inhibitor FR900359 (FR) is unexpectedly efficacious in silencing the signaling of Gq oncoproteins, mutant Gq variants that mostly exist in the active state. These data not only raise the hope that researchers working in drug discovery may be able to potentially strike Gq oncoproteins from the list of undruggable targets, but also raise questions as to how FR achieves its therapeutic effect. Here, we place emphasis on these recent studies and explain why they expand our pharmacological armamentarium for targeting Gq protein oncogenes as well as broaden our mechanistic understanding of Gq protein oncogene function. We also highlight how this novel insight impacts the significance and utility of using G(q) proteins as targets in drug discovery efforts.

Lipid rafts regulate the initiation of cellular metabolic and signaling pathways by organizing the pathway components in ordered microdomains on the cell surface. Cellular responses regulated by lipid rafts range from physiological to pathological, and the success of a therapeutic approach targeting "pathological" lipid rafts depends on the ability of a remedial agent to recognize them and disrupt pathological lipid rafts without affecting normal raft-dependent cellular functions. In this article, concluding the Thematic Review Series on Biology of Lipid Rafts, we review current experimental therapies targeting pathological lipid rafts, including examples of inflammarafts and clusters of apoptotic signaling molecule-enriched rafts. The corrective approaches include regulation of cholesterol and sphingolipid metabolism and membrane trafficking by using HDL and its mimetics, LXR agonists, ABCA1 overexpression, and cyclodextrins, as well as a more targeted intervention with apoA-I binding protein. Among others, we highlight the design of antagonists that target inflammatory receptors only in their activated form of homo- or heterodimers, when receptor dimerization occurs in pathological lipid rafts. Other therapies aim to promote raft-dependent physiological functions, such as augmenting caveolae-dependent tissue repair. The overview of this highly dynamic field will provide readers with a view on the emerging concept of targeting lipid rafts as a therapeutic strategy.

Cholesterol/sphingolipid-rich membrane domains, known as lipid rafts or membrane rafts, play a critical role in the compartmentalization of signaling pathways. Physical segregation of proteins in lipid rafts may modulate the accessibility of proteins to regulatory or effector molecules. Thus, lipid rafts serve as sorting platforms and hubs for signal transduction proteins. Cancer cells contain higher levels of intracellular cholesterol and lipid rafts than their normal non-tumorigenic counterparts. Many signal transduction processes involved in cancer development (insulin-like growth factor system and phosphatidylinositol 3-kinase-AKT) and metastasis [cluster of differentiation (CD)44] are dependent on or modulated by lipid rafts. Additional proteins playing an important role in several malignant cancers (e.g., transmembrane glycoprotein mucin 1) are also being detected in association with lipid rafts, suggesting a major role of lipid rafts in tumor progression. Conversely, lipid rafts also serve as scaffolds for the recruitment and clustering of Fas/CD95 death receptors and downstream signaling molecules leading to cell death-promoting raft platforms. The partition of death receptors and downstream signaling molecules in aggregated lipid rafts has led to the formation of the so-called cluster of apoptotic signaling molecule-enriched rafts, or CASMER, which leads to apoptosis amplification and can be pharmacologically modulated. These death-promoting rafts can be viewed as a linchpin from which apoptotic signals are launched. In this review, we discuss the involvement of lipid rafts in major signaling processes in cancer cells, including cell survival, cell death, and metastasis, and we consider the potential of lipid raft modulation as a promising target in cancer therapy.

Heterotrimeric G proteins are the core upstream elements that transduce and amplify the cellular signals from G protein–coupled receptors (GPCRs) to intracellular effectors. GPCRs are the largest family of membrane proteins encoded in the human genome and are the targets of about one-third of prescription medicines. However, to date, no single therapeutic agent exerts its effects via perturbing heterotrimeric G protein function, despite a plethora of evidence linking G protein malfunction to human disease. Several recent studies have brought to light that the Gq family–specific inhibitor FR900359 (FR) is unexpectedly efficacious in silencing the signaling of Gq oncoproteins, mutant Gq variants that mostly exist in the active state. These data not only raise the hope that researchers working in drug discovery may be able to potentially strike Gq oncoproteins from the list of undruggable targets, but also raise questions as to how FR achieves its therapeutic effect. Here, we place emphasis on these recent studies and explain why they expand our pharmacological armamentarium for targeting Gq protein oncogenes as well as broaden our mechanistic understanding of Gq protein oncogene function. We also highlight how this novel insight impacts the significance and utility of using G(q) proteins as targets in drug discovery efforts.

Antibodies are widely used as cancer therapeutics, but their current use is limited by the low number of antigens restricted to cancer cells. A receptor tyrosine kinase, receptor tyrosine kinase-like orphan receptor 2 (ROR2), is normally expressed only during embryogenesis and is tightly down-regulated in postnatal healthy tissues. However, it is up-regulated in a diverse set of hematologic and solid malignancies, thus ROR2 represents a candidate antigen for antibody-based cancer therapy. Here we describe the affinity maturation and humanization of a rabbit mAb that binds human and mouse ROR2 but not human ROR1 or other human cell-surface antigens. Co-crystallization of the parental rabbit mAb in complex with the human ROR2 kringle domain (hROR2-Kr) guided affinity maturation by heavy-chain complementarity-determining region 3 (HCDR3)-focused mutagenesis and selection. The affinity-matured rabbit mAb was then humanized by complementarity-determining region (CDR) grafting and framework fine tuning and again co-crystallized with hROR2-Kr. We show that the affinity-matured and humanized mAb retains strong affinity and specificity to ROR2 and, following conversion to a T cell–engaging bispecific antibody, has potent cytotoxicity toward ROR2-expressing cells. We anticipate that this humanized affinity-matured mAb will find application for antibody-based cancer therapy of ROR2-expressing neoplasms.