Monica L. Salgado-Lucio, Danelia Ramirez-Ramirez, Coral Y. Jorge-Cruz, Ana L. Roa-Espitia, and Enrique O. Hernandez-Gonzalez

Actin polymerization is a crucial process during sperm capacitation. We have recently described the participation of FAK during actin polymerization in guinea pig spermatozoa. However, the mechanism by which FAK mediates these processes is unknown. Our previous data have shown that MAPK1 (hereafter referred to as ERK2) is activated during the first minutes of capacitation, and inhibition of ERK2 blocked actin polymerization and the acrosome reaction. In this current study, we found that FAK is involved in ERK2 activation – as FAK was phosphorylated at tyrosine residue 925 and bound to Grb2 – and that inhibition of FAK results in a significant decrease of ERK2 activation. We also confirmed the presence of Rho guanine nucleotide exchange factor 2 (ARHGEF2, hereafter referred to as GEF-H1), which is able to associate with RhoA during capacitation. RhoA activation and its participation in actin polymerization were also analyzed. Inhibition of FAK or ERK1/2 impeded GEF-H1 phosphorylation, RhoA activation, and the association between GEF-H1 and RhoA. Finally, we observed the presence of fibronectin on the sperm surface, its role in sperm–sperm interaction as well as participation of β-integrin in the activation of ERK2. Our results show that the signaling pathway downstream of fibronectin, via integrin, FAK, Grb2, MEK1/2, ERK2, GEF-H1 and RhoA regulates the actin polymerization associated with spermatozoa capacitation.

Vaccinia virus (VACV) is a double-stranded DNA virus that devotes a large portion of its 200 kbp genome to suppressing and manipulating the immune response of its host. Here, we investigated how targeted removal of immunomodulatory genes from the VACV genome impacted immune cells in the tumor microenvironment with the intention of improving the therapeutic efficacy of VACV in breast cancer. We performed a head-to-head comparison of six mutant oncolytic VACVs, each harboring deletions in genes that modulate different cellular pathways, such as nucleotide metabolism, apoptosis, inflammation, and chemokine and interferon signaling. We found that even minor changes to the VACV genome can impact the immune cell compartment in the tumor microenvironment. Viral genome modifications had the capacity to alter lymphocytic and myeloid cell compositions in tumors and spleens, PD-1 expression, and the percentages of virus-targeted and tumor-targeted CD8⁺ T cells. We observed that while some gene deletions improved responses in the nonimmunogenic 4T1 tumor model, very little therapeutic improvement was seen in the immunogenic HER2/neu TuBo model with the various genome modifications. We observed that the most promising candidate genes for deletion were those that interfere with interferon signaling. Collectively, this research helped focus attention on the pathways that modulate the immune response in the context of VACV oncolytic virotherapy. They also suggest that the greatest benefits to be obtained with these treatments may not always be seen in "hot tumors."

Background:

Total antioxidant capacity (TAC) reflects an individual's overall antioxidant intake. We sought to clarify whether higher TAC is associated with lower risks of pancreatic cancer incidence and mortality in the U.S. general population.

Sensors being developed by Airbus and a California-based startup might be able to sniff out COVID-19 in an effort to help prevent its spread.

Downing Street has acknowledged there is still a "great deal more to do" to close the gap between capacity and the actual number of Covid-19 tests carried out.

Fewer people would have died from coronavirus in the UK if the country had greater testing capacity sooner, Transport Secretary Grant Shapps has said.

One of the hardest tasks in Earth observation is tracking tiny changes in the shape of the ground.

The team says that after working closely with the local government, infectious disease experts and public health authorities, players will be allowed to access the OVO Athletic Centre starting next week.

Premier League clubs have been warned they may have to wait up to 18 months before they can host capacity crowds again.

Manchester United have put on hold plans for a small increase in capacity at Old Trafford due to coronavirus.

The Secretary of State will be joined at Downing Street with deputy chief medical officer Professor Jonathan Van-Tam.

The funding for services like the RFDS will allow them to evacuate coronavirus patients to larger medical centres and fly in medical workers and equipment for regional respiratory clinics.

An Australian-made ventilator that costs a tenth of the price of existing models is brought to life in just four weeks, which could revolutionise intensive care capability in the fight against COVID-19.

The Canadian military has stripped bases across the country of their uniformed medical personnel to support long-term care homes in Quebec that have been overrun by COVID-19.

Adhesives specialist Intertronics has launched the preeflow eco-DUOMIX, a system that mixes and dispenses two-part materials.

Andreas Johannesson has been announced as Alligator Bioscience’s new interim Chief Financial Officer (CFO), replacing ex-CFO Per-Olof Schrewelius who it was previously confirmed will no longer serve the company.

Johannesson’s career has spanned 15 years in the consumer goods sector, with him managing the finances of firms including TeamOlmed, Stenqvist, Fitness23Seven and Haldex.

He spent a further nine years of his career as a strategic consultant with a focus on consumer goods, five of which were spent at global consulting firm McKinsey & Company.

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The Department of Justice’s Bureau of Justice Assistance today announced the Building Neighborhood Capacity Program Training and Technical Assistance Coordinator Solicitation, part of an innovative approach to build capacity in distressed neighborhoods.

The Department of Justice’s Bureau of Justice Assistance (BJA), together with its partners, the Departments of Housing and Urban Development (HUD), Education, Health and Human Services and Treasury, today announced the selection of the Center for the Study of Social Policy as the Building Neighborhood Capacity Program (BNCP) Training and Technical Assistance Coordinator.

"On behalf of a grateful nation – and America’s entire law enforcement community – it is a privilege to join you in paying tribute, as well as my last respects, to an extraordinary public servant, a key member of the federal law enforcement family, and a true patriot who was always proud to call Seaford his home," said Attorney General Holder.

The Department of Justice’s Bureau of Justice Assistance, on behalf of the White House Neighborhood Revitalization Initiative, today announced the eight neighborhoods that will receive training and technical assistance through the groundbreaking Building Neighborhood Capacity Program.

Alkemist Labs is pleased to announce a move to a new facility with over four times more space to expand capacity and accommodate continued growth.

J&J agrees a manufacturing partnership with Emergent, as it looks to hit its target of one billion doses.

During the high-level meeting with Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland, Tripura and Sikkim, Vardhan appreciated the dedication of all the states in combating COVID-19.

May 5, 2020

The outbreak in Wuhan of the novel coronavirus shows how ragged and disorderly the Chinese police state was in the initial weeks of the pandemic. Beijing’s response was to suppress and manipulate information, at home and abroad. Trump administration officials have painted this as a Chinese plot against the West, but it looks more like a frantic effort by a one-party state to survive a domestic crisis.

May 5, 2020

The outbreak in Wuhan of the novel coronavirus shows how ragged and disorderly the Chinese police state was in the initial weeks of the pandemic. Beijing’s response was to suppress and manipulate information, at home and abroad. Trump administration officials have painted this as a Chinese plot against the West, but it looks more like a frantic effort by a one-party state to survive a domestic crisis.

May 5, 2020

The outbreak in Wuhan of the novel coronavirus shows how ragged and disorderly the Chinese police state was in the initial weeks of the pandemic. Beijing’s response was to suppress and manipulate information, at home and abroad. Trump administration officials have painted this as a Chinese plot against the West, but it looks more like a frantic effort by a one-party state to survive a domestic crisis.

May 5, 2020

The outbreak in Wuhan of the novel coronavirus shows how ragged and disorderly the Chinese police state was in the initial weeks of the pandemic. Beijing’s response was to suppress and manipulate information, at home and abroad. Trump administration officials have painted this as a Chinese plot against the West, but it looks more like a frantic effort by a one-party state to survive a domestic crisis.

Ukraine has been getting a lot of press recently, for all the wrong reasons. In actuality, during the last 25 years, Ukraine has transformed structurally and socially, and even the political changes have been largely positive. Despite its enormous potential, though, Ukraine’s economy has not done well. Per capita GDP has fallen from about $12,000…

The Trump administration’s first three years saw record-setting turnover at the most senior level of the White House staff and the Cabinet. There are also numerous vacancies in Senate-confirmed positions across the executive branch. As of September 22, 2019, the turnover rate among senior White House aides had reached 80 percent, a rate that exceeded…

The United States needs a new strategy for effectively constraining Iran’s future nuclear capabilities. The Trump administration’s current approach has little chance of succeeding. But simply returning the United States to the Joint Comprehensive Plan of Action (JCPOA) is not a long-term solution. By the time the United States would return to the 2015 deal,…

For decades, the United States has sought to constrain Iran’s missile program, both because it poses a conventional military threat to regional stability and because it can provide a delivery capability for nuclear weapons should Iran acquire them. But despite the efforts of the United States and others to impede Iranian procurement of missile-related materials,…

The Trump administration’s “maximum pressure campaign” is putting Iran under great stress, but it is unlikely to compel Tehran to accept its far-reaching demands. The United States needs a new strategy for constraining Iran’s future nuclear capabilities as well as its missile program. Two new Brookings monographs—“Constraining Iran’s Future Nuclear Capabilities” by Robert Einhorn and…

After months of escalating rhetoric demanding that Iran abandon its aspirations to acquire nuclear weapons, the National Intelligence Estimate’s revelation that Iran halted its nuclear weapons program in 2003 comes as quite a shock. Yet again, the capability of the United States intelligence community to assess the nuclear programs of hard targets has been called…

Morocco is making good on it's stated goals of increasing renewable energy development, leading towards 40% of electricity from renewables over the next decade.

According to the International Energy Agency (IEA), by 2018 renewable should overtake natural gas to become the world's second-largest source of energy (oil is #1).

We still need a ton more renewable energy in order to combat climate change, but the good news is that renewable energy is picking up the pace.

The technology could lead to cheaper hydrogen cars in the future.

The country's onward march of low carbon energy shows no signs of stopping.

The British wind energy industry is making huge strides - with more to come.

The Thumb Loop system is designed to meet the maximum wind energy potential of Michigan’s Thumb region as well as contribute to regional system reliability and facilitate wholesale market competition.

West and HealthPrize are collaborating to provide an end to end connected health solution for pharmaceutical companies and the patients they serve.

Bjørnar Tonhaugen of Rystad Energy discusses what could potentially happen to oil prices when the U.S. and the world is projected to run out of viable physical storage capacity, potentially sometime in May.

The city recorded a whopping 510 new COVID-19 positive cases on Monday and another 19 deaths over the past 24 hours. According to civic officials, 10 of the patients who died had co-morbidities and of them, nine were senior citizens.

The Brihanmumbai Municipal Corporation (BMC) has started enhancing the capacity of major hospitals set up for treatment of COVID-19 patients with severe symptoms including Nair, SevenHills and St George Hospitals. Civic officials said that they would be increased in capacity from the current 3,000 beds to 4,750 beds over the next couple of days. As part of the initiative of identifying senior citizens who are at risk of contracting the virus, the civic body has identified 691 senior citizens between April 27 and May 3. All of them have low oxygen saturation problems. They were referred to civic-run and private hospitals in their respective wards for comprehensive treatment.

The number of cases in Dharavi crossed 600 on Monday after 42 new cases were reported in the area. Seven of those cases were from the Matunga labour camp. Four other cases were reported in Dadar and three new cases were reported in Mahim.

Meanwhile, G North ward, which includes areas like Worli and Lower Parel, crossed 800 cases with 60 new cases reported on Monday. Sharad Ughade, assistant municipal commissioner of G North ward, said that the cases were mainly from the BDD chawl and VP Nagar. He added that 30 patients were discharged after full recovery and apart from having the highest number of cases in the city, G North also had the highest number of discharged patients. Meanwhile, a Sena corporator, who holds a position in BMC also tested positive. Civic sources said that she has been admitted to Global Hospital in Parel. State health department officials said that a total of 771 patients tested positive today and 35 deaths were reported in Maharashtra on Monday. The 19 deaths from Mumbai include a resident of Uttar Pradesh. Apart from this, seven deaths were reported in Pune, five in Akola, one each in Solapur, Aurangabad, Thane and Nanded.

Civic body to give jobs to kin of deceased

In view of four BMC workers succumbing to the COVID-19 infection the civic body announced that jobs would be given to their kin. However, they will be assigned based on vacancies of posts like worker, porter, peon and clerk, and also the candidates' educational qualifications.

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The Brihanmumbai Municipal Corporation (BMC) has increased the capacity of Corona Care Centres (CCC) for positive asymptomatic people double fold, with the help of schools, college buildings and pandals on open plots. The city now has 37,343 beds reserved for people who are positive but don't have any symptoms. One-fourth of the city's patients are in these centres. The maximum number of these CCC2 facilities is in wards which are on the top with high numbers of COVID-19 cases.

While the institutional quarantine centres (CCCs) have over 7,000 high-risk contacts with a capacity of little more than 20,000, the BMC is now focusing on the Corona Care Centres 2 (CCC2) which deal with positive asymptomatic patients. The maximum number of facilities is available in E (Byculla), L (Kurla), M east (Govandi, Mankhurd), M west (Chembur) and S (Bhandup) wards where the number of patients is increasing significantly.

With the Shreeniwas Mill building have a capacity of 3,000 beds, two parking lots with 1,000 beds, NSCI club of Worli with 500 beds, and some schools, G south ward has 5,568 beds for asymptomatic positive patients. Byculla has 2,605 beds with an 850 beds centre in a hall and a pandal. With more than 900 cases in Dharavi, G North ward utilised the space of Dharavi College to set up another 700 beds facility. C ward used gymkhana lawns and buildings on Netaji Subhash Road for more than 1,200 beds.

L ward erected pandals in Somaiya ground and Kurla ST Depot for 2,000 beds, M west ward uses the Swami Vivekanand College building for 1,200 beds and M east ward with densely populated slums used MHADA buildings for a 700 beds facility.

As of today, 2,233 people are in CCC2. "Hardly 6 per cent of the beds are occupied so far. But the BMC is preparing for the worst scenario," said a BMC official.

Catch up on all the latest Mumbai news, crime news, current affairs, and a complete guide from food to things to do and events across Mumbai. Also download the new mid-day Android and iOS apps to get latest updates.

Mid-Day is now on Telegram. Click here to join our channel (@middayinfomedialtd) and stay updated with the latest news

Conducted electrical weapons (CEWs), best known by the brand name Taser - have proved to be a generally safe and effective way for law-enforcement officers