Alternative Splicing of the Flip/Flop Cassette and TARP Auxiliary Subunits Engage in a Privileged Relationship That Fine-Tunes AMPA Receptor Gating.

Alternative splicing of AMPA-type glutamate receptors (AMPARs) and allosteric modulation by auxiliary subunits, such as transmembrane AMPAR regulatory proteins (TARPs), are two important mechanisms that regulate the time course of glutamatergic neurotransmission. Prior work has shown that alternative splicing of the flip/flop cassette profoundly regulates TARP γ2 modulation, where flip receptor gating exhibits robust sensitivity to TARPs while flop isoforms are relatively insensitive to TARP modulation. Whether this splice variant-specific regulation extends to other auxiliary subunit families, such as cornichons (CNIHs), GSG1L, or CKAMPs, remains unknown. Here, we demonstrate that CNIH-3 modulation is unaffected by AMPAR alternative splicing due to inherent differences in how CNIH-3 and TARP γ2 modify channel gating. CNIH-3 slows receptor deactivation from the outset of current decay, consistent with structural evidence showing its point of contact at the level of the pore. In contrast, TARP γ2 acts via the KGK site of the ligand-binding domain (LBD) to slow the onset of desensitization. Although GSG1L and CKAMP44 primarily slow recovery from desensitization, their effects on channel gating are unaffected by alternative splicing, further underlining that structural events leading to the onset and recovery from desensitization are separable. Together, this work establishes that alternative splicing and TARP auxiliary subunits form a unique partnership that governs fast glutamatergic signaling at central synapses. Since proteomic studies suggest that all native AMPARs co-assemble with at least two TARPs, allosteric coupling between the flip/flop cassette and TARPs may represent a common design element in all AMPAR complexes of the mammalian brain.SIGNIFICANCE STATEMENT All fast excitatory neurotransmission in the mammalian brain is mediated by AMPA-type glutamate receptors (AMPARs). The time course of AMPAR gating can be regulated by two distinct mechanisms: alternative splicing of the flip/flop cassette and association with auxiliary subunits. Although these regulatory mechanisms have been well studied individually, it is not clear whether alternative splicing impacts auxiliary protein modulation of AMPARs. Here, we compare the four main families of AMPAR auxiliary subunits, transmembrane AMPAR regulatory proteins (TARPs; γ2), cornichons (CNIH-3), GSG1L and CKAMPs (CKAMP44), and find a privileged relationship between TARPs and the flip/flop cassette that is not shared by others. The flop cassette acts as a master switch to override TARP action, and this coupling represents a way to fine-tune AMPAR signaling.

Single-molecule Sequencing of an Animal Mitochondrial Genome Reveals Chloroplast-like Architecture and Repeat-mediated Recombination.

Recent advances in long-read sequencing technology have allowed for single-molecule sequencing of entire mitochondrial genomes, opening the door for direct investigation of the mitochondrial genome architecture and recombination. We used PacBio sequencing to reassemble mitochondrial genomes from two species of New Zealand freshwater snails, Potamopyrgus antipodarum and Potamopyrgus estuarinus. These assemblies revealed a ∼1.7 kb structure within the mitochondrial genomes of both species that was previously undetected by an assembly of short reads and likely corresponding to a large noncoding region commonly present in the mitochondrial genomes. The overall architecture of these Potamopyrgus mitochondrial genomes is reminiscent of the chloroplast genomes of land plants, harboring a large single-copy (LSC) region and a small single-copy (SSC) region separated by a pair of inverted repeats (IRa and IRb). Individual sequencing reads that spanned across the Potamopyrgus IRa-SSC-IRb structure revealed the occurrence of a "flip-flop" recombination. We also detected evidence for two distinct IR haplotypes and recombination between them in wild-caught P. estuarinus, as well as extensive intermolecular recombination between single-nucleotide polymorphisms in the LSC region. The chloroplast-like architecture and repeat-mediated mitochondrial recombination we describe here raise fundamental questions regarding the origins and commonness of inverted repeats in cytoplasmic genomes and their role in mitochondrial genome evolution.

Regulation of iodine-glucose flip-flop in SW1736 anaplastic thyroid cancer cell line.

AIMS AND BACKGROUND: The alternative manner of iodide and glucose uptake found in different types of thyroid cancer, referred to flip-flop. ATC cells indicate low iodide uptake and high glucose uptake, which lack the morphology and genetic characteristics of well-differentiated tumors and become increasingly invasive. Importance placed on the discovery of innovative multi-targeted medicines to suppress the dysregulated signaling in cancer. In this research, we aimed to clarify molecular mechanism of Rutin as a phytomedicine on anaplastic thyroid cancer cell line based on iodide and glucose uptake. MATERIAL METHODS: The MTT test was employed to test cell viability. Iodide uptake assay was performed using a spectrophotometric assay to determine iodide uptake in SW1736 cells based on Sandell-Kolthoff reaction. For glucose uptake detection, ''GOD-PAP'' enzymatic colorimetric assay was applied to measure the direct glucose levels inside of the cells. Determination of NIS, GLUT1 and 3 mRNA expression in SW1736 cells was performed by qRT-PCR. Determination of NIS, GLUT1 and 3 protein levels in SW1736 cells was performed by western blotting. RESULTS: According to our results, Rutin inhibited the viability of SW1736 cells in a time- and dose-dependent manner. Quantitative Real-time RT-PCR analysis exposed that NIS mRNA levels were increased in Rutin treated group compared to the control group. Accordingly, western blot showed high expression of NIS protein and low expression of GLUT 1 and 3 in Rutin treated SW1736 cell line. Rutin increased iodide uptake and decreased glucose uptake in thyroid cancer cell line SW1736 compared to control group. CONCLUSION: Multiple mechanisms point to Rutin's role as a major stimulator of iodide uptake and inhibitor of glucose uptake, including effects at the mRNA and protein levels for both NIS and GLUTs, respectively. Here in, we described the flip-flop phenomenon as a possible therapeutic target for ATC. Moreover, Rutin is first documented here as a NIS expression inducer capable of restoring cell differentiation in SW1736 cell line. It also be concluded that GLUTs as metabolic targets can be blocked specifically by Rutin for thyroid cancer prevention and treatment.

Pharmacokinetic profile and physiological effects of oral and compounded intravenous gabapentin in goats.

OBJECTIVE: To determine the pharmacokinetics and physiological effects following oral and intravenous (IV) administration of gabapentin in goats. STUDY DESIGN: Prospective, crossover study with a 3 week washout period between treatments. ANIMALS: A total of eight healthy, client-owned, female goats. METHODS: Gabapentin (10 mg kg-1) was administered to goats either orally or IV. Gabapentin concentrations were measured in serum samples collected 0-96 hours post-administration using liquid chromatography-quadrupole time-of-flight mass spectrometry. Heart rate, respiratory rate, blood pressure and temperature were recorded before and throughout the study. Correlations of the mean serum concentrations of gabapentin to those of each physiological parameter were determined using the Pearson method. RESULTS: The mean and standard deviation of oral bioavailability for gabapentin was 60.9 ± 11.2%. Maximum serum concentration of gabapentin was lower following oral (1.19 ± 0.29 µg mL-1) than after IV administration (59.76 ± 14.38 µg mL-1, p < 0.0001). Half-lives were longer following PO (8.18 ± 0.57 hours) than after IV administration (1.79 ± 0.06 hours, p < 0.0001). Time to maximum concentration was 6.86 ± 2.27 hours following oral administration. Heart rate was inversely correlated with serum gabapentin concentrations. Slight ataxia was observed in three animals, and one became recumbent following IV gabapentin. CONCLUSIONS AND CLINICAL RELEVANCE: Gabapentin is well-absorbed following oral administration to goats but yielded significantly lower serum concentrations than the IV route. The longer half-life of gabapentin following oral than after IV administration may result from prolonged absorption throughout the caprine gastrointestinal tract. IV gabapentin may cause slight ataxia in some goats.

Quantum Random Access Memory for Dummies.

Quantum Random Access Memory (QRAM) has the potential to revolutionize the area of quantum computing. QRAM uses quantum computing principles to store and modify quantum or classical data efficiently, greatly accelerating a wide range of computer processes. Despite its importance, there is a lack of comprehensive surveys that cover the entire spectrum of QRAM architectures. We fill this gap by providing a comprehensive review of QRAM, emphasizing its significance and viability in existing noisy quantum computers. By drawing comparisons with conventional RAM for ease of understanding, this survey clarifies the fundamental ideas and actions of QRAM. QRAM provides an exponential time advantage compared to its classical counterpart by reading and writing all data at once, which is achieved owing to storage of data in a superposition of states. Overall, we compare six different QRAM technologies in terms of their structure and workings, circuit width and depth, unique qualities, practical implementation, and drawbacks. In general, with the exception of trainable machine learning-based QRAMs, we observe that QRAM has exponential depth/width requirements in terms of the number of qubits/qudits and that most QRAM implementations are practical for superconducting and trapped-ion qubit systems.

Stochastic Adder Circuits with Improved Entropy Output.

Random pulse computing (RPC), the third paradigm along with digital and quantum computing, draws inspiration from biology, particularly the functioning of neurons. Here, we study information processing in random pulse computing circuits intended for the summation of numbers. Based on the information-theoretic merits of entropy budget and relative Kolmogorov-Sinai entropy, we investigate the prior art and propose new circuits: three deterministic adders with significantly improved output entropy and one exact nondeterministic adder that requires much less additional entropy than the previous art. All circuits are realized and tested experimentally, using quantum entropy sources and reconfigurable logic devices. Not only the proposed circuits yield a precise mathematical result and have output entropy near maximum, which satisfies the need for building a programmable random pulse computer, but also they provide affordable hardware options for generating additional entropy.

Effective Parameters Controlling Sterol Transfer: A Time-Resolved Small-Angle Neutron Scattering Study.

Though cholesterol is the most prevalent and essential sterol in mammalian cellular membranes, its precursors, post-synthesis cholesterol products, as well as its oxidized derivatives play many other important physiological roles. Using a non-invasive in situ technique, time-resolved small angle neutron scattering, we report on the rate of membrane desorption and corresponding activation energy for this process for a series of sterol precursors and post-synthesis cholesterol products that vary from cholesterol by the number and position of double bonds in B ring of cholesterol's steroid core. In addition, we report on sterols that have oxidation modifications in ring A and ring B of the steroid core. We find that sterols that differ in position or the number of double bonds in ring B have similar time and energy characteristics, while oxysterols have faster transfer rates and lower activation energies than cholesterol in a manner generally consistent with known sterol characteristics, like Log P, the n-octanol/water partitioning coefficient. We find, however, that membrane/water partitioning which is dependent on lipid-sterol interactions is a better predictor, shown by the correlation of the sterols' tilt modulus with both the desorption rates and activation energy.

Flip-Flop Promotion Mechanisms by Model Transmembrane Peptides.

Lipid transbilayer movement (flip-flop) is regulated by membrane proteins that are involved in homeostasis and signaling in eukaryotic cells. In the plasma membrane, an asymmetric lipid composition is maintained by energy-dependent unidirectional transport. Energy-independent flip-flop promotion by phospholipid scramblases disrupts the asymmetry in several physiological processes, such as apoptosis and blood coagulation. In the endoplasmic reticulum, rapid flip-flop is essential for bilayer integrity because phospholipids are synthesized only in the cytoplasmic leaflet. Phospholipid scramblases are also involved in lipoprotein biogenesis, autophagosome formation, and viral infection. Although several scramblases have been identified and investigated, the precise flip-flop promotion mechanisms are not fully understood. Model transmembrane peptides are valuable tools for investigating the general effects of lipid-peptide interactions. We focus on the development of model transmembrane peptides with flip-flop promotion abilities and their mechanisms.

Low-Voltage and Low-Power True-Single-Phase 16-Transistor Flip-Flop Design.

A low-voltage and low-power true single-phase flip-flop that minimum the total transistor count by using the pass transistor logic circuit scheme is proposed in this paper. Optimization measures lead to a new flip-flop design with better various performances such as speed, power, energy, and layout area. Based on post-layout simulation results using the TSMC CMOS 180 nm and 90 nm technologies, the proposed design achieves the conventional transmission-gate-based flip-flop design with a 53.6% reduction in power consumption and a 63.2% reduction in energy, with 12.5% input data switching activity. In order to further the performance parameters of the proposed design, a shift-register design has been realized. Experimental measurements at 0.5 V/0.5 MHz show that this proposed design reduces power consumption by 47.3% while achieving a layout area reduction of 30.5% compared to the conventional design.

Molecular dynamics simulation study of the positioning and dynamics of α-tocopherol in phospholipid bilayers.

Using molecular dynamics simulations, we investigate the interaction of α-tocopherol (α-toc) with dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylcholine (DMPC), palmitoyloleoylphosphatidylcholine (POPC), and palmitoyloleoylphosphatidylethanolamine (POPE) lipid bilayers. The goal is to develop a better understanding of the positioning and orientation of α-toc inside the bilayers; properties of significant relevance to α-toc anti-oxidant activity. We investigated bilayer systems with 128 lipids in the presence of either single or 14 α-toc molecules. The single α-toc bilayer systems were investigated via biased MD simulations in which the potential of mean force (PMF) and diffusivity were obtained as functions of the distance between α-toc head group and bilayer center. The higher α-toc concentration systems were investigated with unbiased MD simulations. For all four bilayers at both concentrations, the simulations show that the most probable location of the α-toc hydroxyl group is just below the lipid carbonyl group. Overall, the simulation results are in good agreement with existing experimental data except for the DMPC bilayer system for which some experiments predict α-toc to be located closer to bilayer center. The flip-flop frequency calculated shows that the α-toc flip-flop rate is sensitive to bilayer lipid type. In particular, α-toc has a much lower flip-flop rate in a POPE bilayer compared to the three PC lipid bilayers due to the smaller area per lipid in the POPE bilayer. For DMPC and POPC, the α-toc flip-flop rates are significantly higher at higher α-toc concentration and this appears to be related to the local structural disruption caused by α-toc clusters spanning the bilayer.

Deciphering lipid transfer between and within membranes with time-resolved small-angle neutron scattering.

This review focuses on time-resolved neutron scattering, particularly time-resolved small angle neutron scattering (TR-SANS), as a powerful in situ noninvasive technique to investigate intra- and intermembrane transport and distribution of lipids and sterols in lipid membranes. In contrast to using molecular analogues with potentially large chemical tags that can significantly alter transport properties, small angle neutron scattering relies on the relative amounts of the two most abundant isotope forms of hydrogen: protium and deuterium to detect complex membrane architectures and transport processes unambiguously. This review discusses advances in our understanding of the mechanisms that sustain lipid asymmetry in membranes-a key feature of the plasma membrane of cells-as well as the transport of lipids between membranes, which is an essential metabolic process.

Steady state analysis of influx and transbilayer distribution of ergosterol in the yeast plasma membrane.

BACKGROUND: The transbilayer sterol distribution between both plasma membrane (PM) leaflets has long been debated. Recent studies in mammalian cells and in yeast show that the majority of sterol resides in the inner PM leaflet. Since sterol flip-flop in model membranes is rapid and energy-independent, a mechanistic understanding for net enrichment of sterol in one leaflet is lacking. Import of ergosterol in yeast can take place via the ABC transporters Aus1/Pdr11 under anaerobic growth conditions, eventually followed by rapid non-vesicular sterol transport to the endoplasmic reticulum (ER). Little is known about how these transport steps are dynamically coordinated. METHODS: Here, a kinetic steady state model is presented which considers sterol import via Aus1/Pdr11, sterol flip-flop across the PM, bi-molecular complex formation and intracellular sterol release followed by eventual transport to and esterification of sterol in the ER. The steady state flux is calculated, and a thermodynamic analysis of feasibility is presented. RESULTS: It is shown that the steady state sterol flux across the PM can be entirely controlled by irreversible sterol import via Aus1/Pdr11. The transbilayer sterol flux at steady state is a non-linear function of the chemical potential difference of sterol between both leaflets. Non-vesicular release of sterol on the cytoplasmic side of the PM lowers the attainable sterol enrichment in the inner leaflet. Including complex formation of sterol with phospholipids or proteins can explain several puzzling experimental observations; 1) rapid sterol flip-flop across the PM despite net sterol enrichment in one leaflet, 2) a pronounced steady state sterol gradient between PM and ER despite fast non-vesicular sterol exchange between both compartments and 3) a non-linear dependence of ER sterol on ergosterol abundance in the PM. CONCLUSIONS: A steady state model is presented that can account for the observed sterol asymmetry in the yeast PM, the strong sterol gradient between PM and ER and threshold-like expansion of ER sterol for increasing sterol influx into the PM. The model also provides new insight into selective uptake of cholesterol and its homeostasis in mammalian cells, and it provides testable predictions for future experiments.

Flip-flop organization in the chloroplast genome of Capsosiphon fulvescens (Ulvophyceae, Chlorophyta).

To better understand organelle genome evolution of the ulvophycean green alga Capsosiphon fulvescens, we sequenced and characterized its complete chloroplast genome. The circular chloroplast genome was 111,561 bp in length with 31.3% GC content that contained 108 genes including 77 protein-coding genes, two copies of rRNA operons, and 27 tRNAs. In this analysis, we found the two types of isoform, called heteroplasmy, were likely caused by a flip-flop organization. The flip-flop mechanism may have caused structural variation and gene conversion in the chloroplast genome of C. fulvescens. In a phylogenetic analysis based on all available ulvophycean chloroplast genome data, including a new C. fulvescens genome, we found three major conflicting signals for C. fulvescens and its sister taxon Pseudoneochloris marina within 70 individual genes: (i) monophyly with Ulotrichales, (ii) monophyly with Ulvales, and (iii) monophyly with the clade of Ulotrichales and Ulvales. Although the 70-gene concatenated phylogeny supported monophyly with Ulvales for both species, these complex phylogenetic signals of individual genes need further investigations using a data-rich approach (i.e., organelle genome data) from broader taxon sampling.

Single-shot measurement of solids and liquids T1 values by a small-angle flip-flop pulse sequence.

We propose the small-angle flip-flop (SAFF) pulse sequence as an alternative procedure for the rapid measurement of the 1 H spin-lattice relaxation time in the laboratory frame (T1 ) of solid and liquid substances, in a time-domain NMR experiment. Based on the original flip-flop pulse sequence, this technique allows the fast estimation of T1 values of samples that require minutes to hours of acquisition time if traditional pulse sequences are employed. We have applied SAFF to different substances, with T1 ranging from microseconds up to seconds, including natural clays, polymers, and organic and inorganic solvents. We also demonstrate the potential of the pulse sequence in the real-time monitoring of dynamic processes, such as the conformational changes of polymeric materials during heating. The results we obtained with SAFF are comparable with those acquired with the inversion-recovery pulse sequence, with the addition of several benefits. This pulse sequence obeys steady-state and magnetization-conserving principles, making it possible to dismiss the need for relaxation delay times of the order of 5T1 . SAFF has shown high sensitivity in the resolution of individual components of T1 in multiexponential systems and can be easily integrated to well-established pulse sequences, such as Magic Sandwich Echo and Carr-Purcell-Meiboom-Gill, for the single-shot determination of T1 and T2 or T2* .

Evaluation of Interbilayer and Transbilayer Transfer Dynamics of Phospholipids Using Time-Resolved Small-Angle Neutron Scattering.

The bilayer structure of biomembranes consists of thousands of lipids, the composition of which is different for each organelle. Since most lipids are synthesized in the endoplasmic reticulum, subsequent distribution to each organelle determines the composition and function of the biomembranes. Thus, interbilayer transfer and transbilayer movement (flip-flop) of phospholipids play important roles in maintaining homeostasis. A crucial task in biophysics and cell biology is to understand how rapidly lipids migrate between bilayers spontaneously or through proteins and to control these lipid dynamics. Time-resolved small-angle neutron scattering (TR-SANS) is a powerful technique to determine the intervesicular exchange and flip-flop rates of lipids in situ and real time. In this review, I explain how TR-SANS detects the interbilayer and transbilayer transfer of phospholipids and introduce recent progress of my group on the evaluation of spontaneous and protein- (or peptide-)mediated lipid transfer in several phospholipid dispersion systems.

A Radiation-Hardened SAR ADC with Delay-Based Dual Feedback Flip-Flops for Sensor Readout Systems.

For stable and effective control of the sensor system, analog sensor signals such as temperature, pressure, and electromagnetic fields should be accurately measured and converted to digital bits. However, radiation environments, such as space, flight, nuclear power plants, and nuclear fusion reactors, as well as high-reliability applications, such as automotive semiconductor systems, suffer from radiation effects that degrade the performance of the sensor readout system including analog-to-digital converters (ADCs) and cause system malfunctions. This paper investigates an optimal ADC structure in radiation environments and proposes a successive- approximation-register (SAR) ADC using delay-based double feedback flip-flops to enhance the system tolerance against radiation effects, including total ionizing dose (TID) and single event effects (SEE). The proposed flip-flop was fabricated using 130 nm complementary metal-oxide-semiconductor (CMOS) silicon-on-insulator (SOI) process, and its radiation tolerance was measured in actual radiation test facilities. Also, the proposed radiation-hardened SAR ADC with delay-based dual feedback flip-flops was designed and verified by utilizing compact transistor models, which reflect radiation effects to CMOS parameters, and radiation simulator computer aided design (CAD) tools.

Formation of asymmetric vesicles via phospholipase D-mediated transphosphatidylation.

Most biomembranes have an asymmetric structure with regard to phospholipid distribution between the inner and outer leaflets of the lipid bilayers. Control of the asymmetric distribution plays a pivotal role in several cellular functions such as intracellular membrane fusion and cell division. The mechanism by which membrane asymmetry and its alteration function in these transformation processes is not yet clear. To understand the significance of membrane asymmetry on trafficking and metabolism of intracellular vesicular components, a system that experimentally reproduces the asymmetric nature of biomembranes is essential. Here, we succeeded in obtaining asymmetric vesicles by means of transphosphatidylation reactions with phospholipase D (PLD), which acts exclusively on phosphatidylcholine (PC) present in the outer leaflet of vesicles. By treating PC vesicles with PLD in the presence of 1.7M serine and 0.3M ethanolamine, we obtained asymmetric vesicles that are topologically similar to intracellular vesicles containing phosphatidylserine and phosphatidylethanolamine in the cytosolic leaflet. PLD and other unwanted compounds could be removed by trypsin digestion followed by dialysis. Our established technique has a great advantage over conventional methods in that asymmetric vesicles can be provided at high yield and high efficiency, which is requisite for most physicochemical assays.

Genetic variants demonstrating flip-flop phenomenon and breast cancer risk prediction among women of African ancestry.

BACKGROUND: Few studies have evaluated the performance of existing breast cancer risk prediction models among women of African ancestry. In replication studies of genetic variants, a change in direction of the risk association is a common phenomenon. Termed flip-flop, it means that a variant is risk factor in one population but protective in another, affecting the performance of risk prediction models. METHODS: We used data from the genome-wide association study (GWAS) of breast cancer in the African diaspora (The Root consortium), which included 3686 participants of African ancestry from Nigeria, USA, and Barbados. Polygenic risk scores (PRSs) were constructed from the published odds ratios (ORs) of four sets of susceptibility loci for breast cancer. Discrimination capacity was measured using the area under the receiver operating characteristic curve (AUC). RESULTS: Flip-flop phenomenon was observed among 30~40% of variants across studies. Using the 34 variants with consistent directionality among previous studies, we constructed a PRS with AUC of 0.531 (95% confidence interval [CI]: 0.512-0.550), which is similar to the PRS using 93 variants and ORs from European ancestry populations (AUC = 0.525, 95% CI: 0.506-0.544). Additionally, we found the 34-variant PRS has good discriminative accuracy in women with family history of breast cancer (AUC = 0.586, 95% CI: 0.532-0.640). CONCLUSIONS: We found that PRS based on variants identified from prior GWASs conducted in women of European and Asian ancestries did not provide a comparable degree of risk stratification for women of African ancestry. Further large-scale fine-mapping studies in African ancestry populations are desirable to discover population-specific genetic risk variants.

Libration of phenyl groups detected by VT-SSNMR: Comparison with X-ray crystallography.

The X-ray crystal structure of 2-benzyl-1H-benzimidazole, 2BnBzIm, was determined at 293 K showing no dynamic phenomena (disorder) of any class. On the other hand, some 13 C NMR signals were absent in the CPMAS spectrum (100 MHz, 300 K). We decided to carry out variable-temperature SSNMR and discovered that the missing signals are ortho and meta carbons of the phenyl ring of the benzyl group. Line-shape analysis and the Eyring equation were used to determine the barrier, which was compared with the calculated DFT for the gas phase that it is much lower.

Update of Single Event Effects Radiation Hardness Assurance of Readout Integrated Circuit of Infrared Image Sensors at Cryogenic Temperature.

This paper review presents Single Event Effects (SEE) irradiation tests under heavy ions of the test-chip of D-Flip-Flop (DFF) cells and complete readout integrated circuits (ROIC) as a function of temperature, down to 50 K. The analyses of the experimental data are completed using the SEE prediction tool MUSCA SEP3. The conclusions derived from the experimental measurements and related analyses allow to update the current SEE radiation hardness assurance (RHA) for readout integrated circuits of infrared image sensors used at cryogenic temperatures. The current RHA update is performed on SEE irradiation tests at room temperature, as opposed to the operational cryogenic temperature. These tests include SET (Single Event Transient), SEU (Single Event Upset) and SEFI (Single Event Functional Interrupt) irradiation tests. This update allows for reducing the cost of ROIC qualifications and the test setup complexity for each space mission.