Tariff round 2021 The fight for the collective agreement

Status: 15.06.2021 12:43 p.m.

The economy in Germany will recover in 2021 after the slump as a result of the pandemic. The unions are now calling for some significant wage increases. Your goals and the collective bargaining agreements for 2021 at a glance. Falling numbers of new corona infections and the progress made in vaccination will lead to an economic recovery in Germany in 2021. The growing global economy supports the demand for goods “Made in Germany”. At the same time, inflation is rising significantly. With their sometimes high demands, the unions want all the more to ensure that the collective bargaining agreements in 2021 do not result in any real wage losses for employees.

background 06/18/2021

The trade unions and employers naturally assess the scope for wage increases differently in this situation. Collective bargaining is therefore programmed. You can find an overview of the major collective bargaining rounds in 2021 here:

* Source: WSI tariff archive; Note d. Red .: The table only shows the percentage wage claims and collective bargaining agreements. We have not listed special regulations such as one-off payments, profit sharing, wage increases by fixed sums (for all employees regardless of the respective income), vacation, etc. in order to keep the table clearer and comparable.

Celestial flower In order to buy Thien Ly flowers, you probably have to go to the market instead of just going to the supermarket because this flower is rarely sold in supermarkets, no matter how big or small. 1. Stir-fried Celestial Flowers with Eggs Stir-fried angelica flowers with eggs Ingredients to be prepared – 200g Thien Ly flower hoa – 2 eggs – 2 sprigs of scallions – Spices: Oyster oil, salt, seasoning How to make fried angelica flowers with eggs – Step 1: Prepare the ingredients You wash the flowers with water, then soak the flowers in a dilute salt water mixture for about 5 minutes. Rinse with water again and then let the vegetables drain. The flowers are very small, so soaking the flowers in dilute salt water combined with a little strong hand washing will help you remove all the dirt on the flowers. Crack 2 eggs into a bowl, add 1/2 teaspoon pepper and 1/2 teaspoon salt and stir well. Beat eggs with a little salt and pepper Onions you wash, cut into small pieces. – Step 2: Stir-fry Thien Ly flower with eggs You put 1 teaspoon of cooking oil in the pan, wait for the oil to be hot, then pour the natural flowers into 1 teaspoon of oyster sauce, stir for about 1 minute on low heat. Turn around for a while, you will see the flower of the lily collapse Next, put the bowl of beaten eggs and spices in the pan and stir until the eggs are firm. Add the chopped scallions to the pan, season to taste and stir for about 15 seconds. It is done! It only takes about 2 minutes for you to complete this egg fried natural flower dish! 2. Celery flowers stir-fried with beef Stir-fried Angelica flowers with beef Ingredients to be prepared – 300g beef – 200g Thien Ly flower hoa – 3 cloves of garlic – Seasoning: Oyster oil, sesame oil, seasoning, salt, pepper How to make stir-fried angelica flowers with beef – Step 1: Prepare the ingredients You wash the natural flowers and then soak the flowers in a dilute salt water mixture for about 5 minutes, then take them out, rinse with water and dry. Peeled garlic, minced. Wash the beef and cut it into bite-sized pieces. Put the meat in a bowl with 1/2 teaspoon of pepper, 1/2 teaspoon of sesame oil, 1/2 of the minced garlic and 1/2 teaspoon of salt, mix well and marinate for 5-8 minutes. Marinate beef with sesame oil, garlic, salt and pepper. – Step 2: Stir-fry beef with Thien Ly flower You put 1 teaspoon of cooking oil in the pan and saute the remaining minced garlic. When the garlic is fragrant, add the marinated beef bowl and stir until the meat is tender. Remove the meat to a separate bowl. Stir-fry beef first Next, you use the same pan that just turned the beef to stir-fry the heavenly flowers. Add the flowers and stir over low heat for about 1 minute for the flowers to deflate. Stir-fry beef and flowers separately Add 1 teaspoon of oyster sauce, 1/2 teaspoon of seasoning to the pan with the previously sautéed beef, stir for about 1-2 minutes over medium heat and then turn off the heat. That’s it, the fried beef with Thien Ly flower! Excluding the time to marinate the meat, this stir-fried beef with flowers will only take you 3-4 minutes. 3. Crab soup cooked with heavenly flowers Crab soup cooked with heavenly flowers is both quick and delicious Ingredients to be prepared – 200g of minced crab – 100g of Thien Ly flower – Spices: Salt, seasoning, shrimp paste How to cook crab soup with angelica flowers – Step 1: Filter crabs To save time and effort, you can buy pre-ground crab in the supermarket or in the market. Then, put the crushed crab into a large bowl with 500ml of water, stir well with chopsticks and filter through a sieve to remove the residue. You can filter the crab twice as above to get all the juice. Filter the crab twice, each time for about 400-500ml of water – Step 2: Cook crab soup Before cooking crab soup, don’t forget to wash the flowers and let them dry! You put the filtered crab juice into the pot, cover the pot and cook on medium heat for about 2 minutes. At this point, you will see pieces of crab bricks in the pot. You gently drop the washed natural herbs into the pot with 1 teaspoon of seasoning seeds, 1/2 teaspoon of salt. Use a ladle to gently stir the spices and flowers, do not stir vigorously to avoid breaking the crab bricks. Reduce the heat, cook for about 3 more minutes and you’ve finished the crab soup cooked with heavenly flowers. Before scooping the soup into the bowl, don’t forget to taste the seasoning to taste! Some of the uses of natural flowers that you may not know 1. Supports weight loss The reason why natural flowers have a weight loss effect is because this flower contains a lot of fiber, chlorophyll, and very few calories. According to the research of modern medicine: Each branch of natural flower contains 3% fiber, 2.8% protein. In addition, it also contains carbohydrates, vitamins C/B1/B2/PP and provitamin A (carotene) and other minerals such as phosphorus, iron and especially zinc. Therefore, when eating dishes made from natural flowers will bring a feeling of fullness, limit fat absorption, so it will effectively support weight loss for overweight and obese people. 2. Support people with hemorrhoids Natural flowers are a type of food that has a cooling effect. Therefore, Thien Ly flower is also known as a very good food for people with hemorrhoids. Moreover, this flower also has strong natural antiseptic properties, helping to eliminate bacteria and prevent inflammation. The components present in the flower of sage also have the effect of speeding up wound healing. With these information and suggestions, I hope you will have more ways to make Thien Ly flowers into dishes that are both delicious, easy to make and healthy! According to the Vietnamese life

As reflected in the name of TIM-3, current research on it is mainly focused on T cells. TIM-3 is regarded as a marker molecule of T cell exhaustion in chronic viral infection and cancer models[2].

Although multiple drugs targeting TIM-3 have entered clinical trials[1], but The mechanism of blocking TIM-3’s anti-tumor activity is still a bit vague Because TIM-3 is also expressed on many other immune cells, do immune cells other than T cells participate in its anti-cancer effect, or even play a more important role?

On June 9, 2021, the Vijay K. Kuchroo team from Harvard Medical School published important research results in the journal Nature. They found Blocking TIM-3 on dendritic cells (DCs) may play a more critical role in enhancing anti-tumor immunity [3]!

Screenshot of the paper’s homepage

In order to understand the specific functional mechanism of TIM-3, the researchers used a large number of conditional knockout mouse models.They found that in After knocking out TIM-3 in CD4 and CD8+ T cells at the same time, tumor growth was inhibited to a certain extent, but not very significant ;and Specific knockout of TIM-3 in CD8+ T cells, regulatory T cells or NK cells does not affect tumor growth .

This result is a bit surprising, but the researchers quickly thought, would TIM-3 on myeloid cells have a more important function?

The researchers found through single-cell sequencing combined with flow cytometry that High expression of TIM-3 in DC1s and migDCs (migDCs) in tumors .in After specifically knocking out TIM-3 in DCs, tumor growth was significantly inhibited, and This effect is stronger than TIM-3 knocking out T cells .

Knock out TIM-3 in dendritic cells (gene name is Havcr2), the tumor is significantly suppressed

So, how does TIM-3 on DCs affect the anti-tumor immune response?

With the help of single-cell sequencing results, the researchers found that after knocking out TIM-3 in DCs, the number of CD8+ T cells infiltrated in the tumor increased. A more detailed analysis found that Early activation, effect, memory, memory precursor T cells increased , These T cells play a key role in the anti-tumor immune response[4].

Streaming analysis also confirmed that in After conditionally knocking out the TIM-3 of DCs, the memory precursor CD8+ T cells and effector T cells infiltrated in the tumor increased significantly .

After knocking out TIM-3 of DCs, memory precursor CD8+ T cells (TCF1) and effector T cells (CX3CR1, T-bet, Ki67) increased

One of the main functions of DCs is to promote the anti-tumor immune function of antigen-specific CD8+ T cells through antigen presentation[5].Further analyzing the myeloid cells in single-cell sequencing, the researchers found Some genes related to MHC class I antigen presentation are significantly elevated .

Mouse experiments also confirmed that after knocking out the TIM-3 of DCs, the proportion of antigen-specific CD8+ T cells in the tumor was significantly increased, and it had a stronger killing potential.Description Inhibition of TIM-3 can enhance antigen-specific immune response .

After knocking out the TIM-3 of DCs, the proportion of antigen-specific CD8+ T cells increases and has a stronger killing potential

After studying the mechanism at the cellular level, the researchers began to further explore more detailed molecular mechanisms.

The researchers first analyzed the interaction between CD8+ T cells and DCs based on single-cell sequencing technology. The results showed that after knocking out the TIM-3 of DCs, the ligand-receptor interaction scores of Il18–Il18r1 and Il18–Il18rap increased significantly.Analysis of cytokines in tumor homogenate also found Significantly increased levels of IL-1β and IL-18 .

Friends who are familiar with inflammasomes must be able to think that inflammasomes mediate the activation and release of IL-1β and IL-18. Does knocking out TIM-3 activate the inflammasomes?

Pattern diagram of inflammasome activation[6]

Sure enough, analyzing single-cell sequencing data, the researchers found that in the TIM-3 knockout DCs, inflammasome-related gene characteristics were significantly enriched.

Inflammasomes can be activated by pathogen-related molecular patterns (PAMP) and damage-related molecular patterns (DAMP)[7]Since the research here did not involve pathogens, researchers naturally wondered whether endogenous DAMP (such as reactive oxygen species, oxidized lipids, and oxidized DNA) activated the inflammasomes?

Researchers found that in TIM-3 knock-out DCs, the enrichment level of oxidative stress-related gene characteristics was significantly increased, and flow analysis also confirmed Increased ROS levels in DC1s and mDCs .Furthermore, the researchers treated mice with tumors with antioxidants (N-acetylcysteine) and found that The tumor suppressor effect brought by knocking out TIM-3 is completely eliminated, and the increase in IL-1β levels in the tumor is also completely eliminated .

After knocking out TIM-3, the level of ROS in DC1s and migDCs increased

So, is the activation of the inflammasome pathway the reason for the enhanced anti-tumor immune response?

Researchers used three ways to inhibit the inflammasome pathway (inhibition of caspase1, inhibition of NLRP3 inflammasome, inhibition of IL-1β/IL-18, friends can check the above schematic diagram), and found The anti-tumor effect enhanced by knocking out TIM-3 completely disappears, and the function-enhancing effect of CD8+ T cells is also eliminated .

Inhibition of the inflammasome pathway can eliminate the immune enhancement effect of blocking TIM-3

Overall, this study found that compared to T cells, TIM-3 on DCs may play a more critical role in tumor immunity , This discovery has a certain subversive significance to people’s previous cognition.

The author analyzes the mechanism from the perspectives of cell function changes in the tumor microenvironment and changes in molecular pathways in DCs, but this article still leaves many unanswered questions.

For example, how does knocking out TIM-3 lead to increased levels of oxidative stress in DCs? In addition, the experimental evidence of the relationship between oxidative stress and inflammasome activation in this article is still weak. In this model, is it possible that the inflammasome may be activated by other factors?

How does the activation of inflammasome affect the function of DCs and T cells? Is it possible that TIM-3 may affect the function of DCs through other mechanisms?For example, in the latest issue of Immunity, Brian Ruffell and others believe that Blocking TIM-3 contributes to the activation of the cGAS-STING pathway in DCs, thereby promoting the anti-tumor immune response [8].

Although TIM-3 still has a lot to be studied, it is worth looking forward to that many TIM-3 antibodies have entered clinical trials, including some domestic drugs. It is hoped that these drugs can be marketed as soon as possible and benefit more patients.

references

1. Siddiqui I, Schaeuble K, Chennupati V, et al. Intratumoral Tcf1(+)PD-1(+)CD8(+) T Cells with Stem-like Properties Promote Tumor Control in Response to Vaccination and Checkpoint Blockade Immunotherapy. Immunity. Jan 15 2019;50(1):195-211 e10. doi:10.1016/j.immuni.2018.12.021

2. Roberts EW, Broz ML, Binnewies M, et al. Critical Role for CD103(+)/CD141(+) Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma. Cancer Cell. Aug 8 2016; 30(2):324-336. doi:10.1016/j.ccell.2016.06.003

3. Terlizzi M, Casolaro V, Pinto A, Sorrentino R. Inflammasome: cancer’s friend or foe? Pharmacol Ther. Jul 2014;143(1):24-33. doi:10.1016/j.pharmthera.2014.02.002

4. de Mingo Pulido A, Hanggi K, Celias DP, et al. The inhibitory receptor TIM-3 limits activation of the cGAS-STING pathway in intra-tumoral dendritic cells by suppressing extracellular DNA uptake. Immunity. Jun 8 2021;54( 6):1154-1167 e7. doi:10.1016/j.immuni.2021.04.019